Micro/nano encapsulation in pharmaceutical/nutraceutical field
The encapsulation of drugs or other active molecules is fundamental: to prolong release of pesticides and herbicides in the agriculture field; to enclose spices in the food industry; to incorporate essences, vitamins, and solar filters in the field of cosmetics; and to modify release of drugs from dosage systems in pharmaceutical manufacturing.
In the pharmaceutical/nutraceutical field, the full success of pharmacological therapies is strongly dependent on the use of suitable, efficient and smart drug delivery systems (DDSs). Micro and nano vectors can act as controlled drug delivery systems, allowing a sustained release to the target site, minimizing drug loss or degradation and reducing side effects.
Nano carriers, which are preferred in the case of intravenous administration, can be accumulated in tumor tissues by permeating through membrane fenestrations of tumor blood vessels thanks to the passive targeting mechanism. On the other hand, micro carriers, preferred for topical and oral applications, can assure larger drug loading capacities, keeping a low toxicity, over single-unit dosage forms.
Both can be achieved by the same processes, by adjusting some experimental conditions on the basis of both the materials features and the final desired properties, i. e. the particles size, the structure, the external charge.
Do you want to know more about polymeric micro and nano carriers? Read this.
Do you want to know more about liposomes? Read this.
Research lines
The TPP group is involved in the development of production processes and characterization of both lipid and polymeric, micro and nano systems encapsulating active molecules, obtained by both modified conventional techniques, i.e. double emulsions, and innovative techniques, using alternative energy resources, such as ultrasonic atomization, eventually coupled with microwave drying. Our research can be summarized as:
Micro and nano systems production
- Polymeric micro systems formation through ultrasound assisted atomization
- Polymeric microspheres formation through double emulsion
- Polymeric nanospheres formation through multiple emulsion
- Micro and nano liposomes formation through the thin film hydration technique followed by a size reduction process based on duty cycle sonication.
Micro and nano systems characterization
- Analysis of the active principle release
- Stability test of delivery systems
- Analytical quantification
- Gravimetric techniques, image and texture analysis
Implants planning for micro and nano systems production
- Single-pot semicontinuous bench scale apparatus to produce micro particles
- Single-pot semicontinuous bench scale apparatus to produce liposomes
Related publications:
Read More
2022
Caccavo, Diego; Della Vecchia, Marica ; Barba, Anna Angela; Lamberti, Gaetano
Simil-microfluidic ethanol injection mixer for the continuous synthesis production of liposomes: laminar vs turbulent regime Inproceedings
CHISA - Prague (Czech Republic), 2022.
@inproceedings{Caccavo2022,
title = {Simil-microfluidic ethanol injection mixer for the continuous synthesis production of liposomes: laminar vs turbulent regime},
author = {Diego Caccavo and Marica {Della Vecchia} and Anna Angela Barba and Gaetano Lamberti},
year = {2022},
date = {2022-08-23},
booktitle = {CHISA - Prague (Czech Republic)},
keywords = {},
pubstate = {published},
tppubtype = {inproceedings}
}
2019
Barba, Anna Angela; Bochicchio, Sabrina; Dalmoro, Annalisa; Lamberti, Gaetano
Lipid Delivery Systems for Nucleic-Acid-Based-Drugs: From Production to Clinical Applications Journal Article
Pharmaceutics, 11 (360), 2019.
@article{Barba2019,
title = {Lipid Delivery Systems for Nucleic-Acid-Based-Drugs: From Production to Clinical Applications},
author = {Anna Angela Barba and Sabrina Bochicchio and Annalisa Dalmoro and Gaetano Lamberti},
url = {https://www.mdpi.com/1999-4923/11/8/360},
doi = {10.3390/pharmaceutics11080360},
year = {2019},
date = {2019-07-24},
journal = {Pharmaceutics},
volume = {11},
number = {360},
abstract = {In the last years the rapid development of Nucleic Acid Based Drugs (NABDs) to be used in gene therapy has had a great impact in the medical field, holding enormous promise, becoming “the latest generation medicine” with the first ever siRNA-lipid based formulation approved by the United States Food and Drug Administration (FDA) for human use, and currently on the market under the trade name Onpattro™. The growth of such powerful biologic therapeutics has gone hand in hand with the progress in delivery systems technology, which is absolutely required to improve their safety and effectiveness. Lipid carrier systems, particularly liposomes, have been proven to be the most suitable vehicles meeting NABDs requirements in the medical healthcare framework, limiting their toxicity, and ensuring their delivery and expression into the target tissues. In this review, after a description of the several kinds of liposomes structures and formulations used for in vitro or in vivo NABDs delivery, the broad range of siRNA-liposomes production techniques are discussed in the light of the latest technological progresses. Then, the current status of siRNA-lipid delivery systems in clinical trials is addressed, offering an updated overview on the clinical goals and the next challenges of this new class of therapeutics which will soon replace traditional drugs},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In the last years the rapid development of Nucleic Acid Based Drugs (NABDs) to be used in gene therapy has had a great impact in the medical field, holding enormous promise, becoming “the latest generation medicine” with the first ever siRNA-lipid based formulation approved by the United States Food and Drug Administration (FDA) for human use, and currently on the market under the trade name Onpattro™. The growth of such powerful biologic therapeutics has gone hand in hand with the progress in delivery systems technology, which is absolutely required to improve their safety and effectiveness. Lipid carrier systems, particularly liposomes, have been proven to be the most suitable vehicles meeting NABDs requirements in the medical healthcare framework, limiting their toxicity, and ensuring their delivery and expression into the target tissues. In this review, after a description of the several kinds of liposomes structures and formulations used for in vitro or in vivo NABDs delivery, the broad range of siRNA-liposomes production techniques are discussed in the light of the latest technological progresses. Then, the current status of siRNA-lipid delivery systems in clinical trials is addressed, offering an updated overview on the clinical goals and the next challenges of this new class of therapeutics which will soon replace traditional drugsDalmoro, Annalisa; Bochicchio, Sabrina; Lamberti, Gaetano; Bertoncin, Paolo; Janssens, Barbara; Barba, Anna Angela
Micronutrients encapsulation in enhanced nanoliposomal carriers by a novel preparative technology Journal Article
RSC Advances, 9 , pp. 19800-19812, 2019.
@article{Dalmoro2019,
title = {Micronutrients encapsulation in enhanced nanoliposomal carriers by a novel preparative technology },
author = {Annalisa Dalmoro and Sabrina Bochicchio and Gaetano Lamberti and Paolo Bertoncin and Barbara Janssens and Anna Angela Barba},
url = {https://pubs.rsc.org/en/content/articlelanding/2019/ra/c9ra03022k},
doi = {10.1039/C9RA03022K},
year = {2019},
date = {2019-06-25},
journal = {RSC Advances},
volume = {9},
pages = {19800-19812},
abstract = {Micronutrients administration by fortification of staple and complementary foods is a followed strategy to fight malnutrition and micronutrient deficiencies and related pathologies. There is a great industrial interest in preparation of formulations for joint administration of vitamin D3 and vitamin K2 for providing bone support, promoting heart health and helping boost immunity. To respond to this topic, in this work, uncoated nanoliposomes loaded with vitamin D3 and K2 were successfully prepared, by using a novel, high-yield and semi continuous technique based on simil-microfluidic principles. By the same technique, to promote and to enhance mucoadhesiveness and stability of the produced liposomal structures, chitosan was tested as covering material. By this way polymer\textendashlipid hybrid nanoparticles, encapsulating vitamin D3 and vitamin K2, with improved features in terms of stability, loading and mucoadhesiveness were produced for potential nutraceutical and pharmaceutical applications.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Micronutrients administration by fortification of staple and complementary foods is a followed strategy to fight malnutrition and micronutrient deficiencies and related pathologies. There is a great industrial interest in preparation of formulations for joint administration of vitamin D3 and vitamin K2 for providing bone support, promoting heart health and helping boost immunity. To respond to this topic, in this work, uncoated nanoliposomes loaded with vitamin D3 and K2 were successfully prepared, by using a novel, high-yield and semi continuous technique based on simil-microfluidic principles. By the same technique, to promote and to enhance mucoadhesiveness and stability of the produced liposomal structures, chitosan was tested as covering material. By this way polymer–lipid hybrid nanoparticles, encapsulating vitamin D3 and vitamin K2, with improved features in terms of stability, loading and mucoadhesiveness were produced for potential nutraceutical and pharmaceutical applications.2018
Bochicchio, Sabrina; Dalmoro, Annalisa; Bertoncin, Paolo; Lamberti, Gaetano; Moustafine, Rouslan I; Barba, Anna Angela
Design and production of hybrid nanoparticles with polymeric-lipid shell–core structures: conventional and next-generation approaches Journal Article
RSC Advances, 8 , pp. 34614–34624, 2018.
@article{Bochicchio2018,
title = {Design and production of hybrid nanoparticles with polymeric-lipid shell\textendashcore structures: conventional and next-generation approaches},
author = {Sabrina Bochicchio and Annalisa Dalmoro and Paolo Bertoncin and Gaetano Lamberti and Rouslan I. Moustafine and Anna Angela Barba },
url = {https://pubs.rsc.org/en/Content/ArticleLanding/2018/RA/C8RA07069E#!divAbstract},
doi = {10.1039/c8ra07069e},
year = {2018},
date = {2018-09-27},
journal = {RSC Advances},
volume = {8},
pages = {34614\textendash34624},
abstract = {Liposomes constitute a class of prominent drug delivery systems due their cell-mimetic behaviour. Despite
their high biocompatibility, biodegradability and low intrinsic toxicity, their poor stability in biological fluids
as well as in stock conditions (high tendency to degrade or aggregate) have led to new approaches for
liposome stabilization (e.g., surface covering with polymers). Here, liposomes were enwrapped by the
natural biocompatible polymer chitosan to achieve stable shell\textendashcore nanostructures. Covered
nanoliposomes were produced using an innovative continuous method based on microfluidic principles.
The produced hybrid polymeric-lipid nanoparticles were characterized in terms of structural properties,
size and stability. Moreover, phenomenological aspects in formation of nanoliposomal vesicles and
chitosan layering, product quality (structure, size) and manufacturing yield related to this novel method
were compared with those of the conventional dropwise method and the obtained products. The
proposed simil-microfluidic method led to the production of stable and completely chitosan-covered
liposomes with a shell\textendashcore nanostructure that avoided the disadvantages inherent in the conventional
method (which are time-consuming and/or require bulky and more expensive equipment).},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Liposomes constitute a class of prominent drug delivery systems due their cell-mimetic behaviour. Despite
their high biocompatibility, biodegradability and low intrinsic toxicity, their poor stability in biological fluids
as well as in stock conditions (high tendency to degrade or aggregate) have led to new approaches for
liposome stabilization (e.g., surface covering with polymers). Here, liposomes were enwrapped by the
natural biocompatible polymer chitosan to achieve stable shell–core nanostructures. Covered
nanoliposomes were produced using an innovative continuous method based on microfluidic principles.
The produced hybrid polymeric-lipid nanoparticles were characterized in terms of structural properties,
size and stability. Moreover, phenomenological aspects in formation of nanoliposomal vesicles and
chitosan layering, product quality (structure, size) and manufacturing yield related to this novel method
were compared with those of the conventional dropwise method and the obtained products. The
proposed simil-microfluidic method led to the production of stable and completely chitosan-covered
liposomes with a shell–core nanostructure that avoided the disadvantages inherent in the conventional
method (which are time-consuming and/or require bulky and more expensive equipment).Dalmoro, Annalisa; Bochicchio, Sabrina; Nasibullin, Shamil F; Bertoncin, Paolo; Lamberti, Gaetano; Barba, Anna Angela; Moustafine, Rouslan I
Polymer-lipid hybrid nanoparticles as enhanced indomethacin delivery systems Journal Article
European Journal of Pharmaceutical Sciences, 121 , pp. 16-28, 2018.
@article{Dalmoro2018b,
title = {Polymer-lipid hybrid nanoparticles as enhanced indomethacin delivery systems},
author = {Annalisa Dalmoro and Sabrina Bochicchio and Shamil F. Nasibullin and Paolo Bertoncin and Gaetano Lamberti and Anna Angela Barba and Rouslan I. Moustafine},
url = {https://www.sciencedirect.com/science/article/pii/S0928098718302331},
doi = {10.1016/j.ejps.2018.05.014},
year = {2018},
date = {2018-08-30},
journal = {European Journal of Pharmaceutical Sciences},
volume = {121},
pages = {16-28},
abstract = {Non-steroidal anti-inflammatory drugs (NSAIDs), i.e. indomethacin used for rheumatoid arthritis and non-rheumatoid inflammatory diseases, are known for their injurious actions on the gastrointestinal (GI) tract. Mucosal damage can be avoided by using nanoscale systems composed by a combination of liposomes and biodegradable natural polymer, i.e. chitosan, for enhancing drug activity.
Aim of this study was to prepare chitosan-lipid hybrid delivery systems for indomethacin dosage through a novel continuous method based on microfluidic principles. The drop-wise conventional method was also applied in order to investigate the effect of the two polymeric coverage processes on the nanostructures features and their interactions with indomethacin. Thermal-physical properties, mucoadhesiveness, drug entrapment efficiency, in vitro release behavior in simulated GI fluids and stability in stocking conditions were assayed and compared, respectively, for the uncoated and chitosan-coated nanoliposomes prepared by the two introduced methods.
The prepared chitosan-lipid hybrid structures, with nanometric size, have shown high indomethacin loading (about 10%) and drug encapsulation efficiency up to 99%. TEM investigation has highlighted that the developed novel simil-microfluidic method is able to put a polymeric layer, surrounding indomethacin loaded nanoliposomes, thicker and smoother than that achievable by the drop-wise method, improving their storage stability. Finally, double pH tests have confirmed that the chitosan-lipid hybrid nanostructures have a gastro retentive behavior in simulated gastric and intestinal fluids thus can be used as delivery systems for the oral-controlled release of indomethacin.
Based on the present results, the simil-microfluidic method, working with large volumes, in a rapid manner, without the use of drastic conditions and with a precise control over the covering process, seems to be the most promising method for the production of suitable indomethacin delivery system, with a great potential in industrial manufacturing.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Non-steroidal anti-inflammatory drugs (NSAIDs), i.e. indomethacin used for rheumatoid arthritis and non-rheumatoid inflammatory diseases, are known for their injurious actions on the gastrointestinal (GI) tract. Mucosal damage can be avoided by using nanoscale systems composed by a combination of liposomes and biodegradable natural polymer, i.e. chitosan, for enhancing drug activity.
Aim of this study was to prepare chitosan-lipid hybrid delivery systems for indomethacin dosage through a novel continuous method based on microfluidic principles. The drop-wise conventional method was also applied in order to investigate the effect of the two polymeric coverage processes on the nanostructures features and their interactions with indomethacin. Thermal-physical properties, mucoadhesiveness, drug entrapment efficiency, in vitro release behavior in simulated GI fluids and stability in stocking conditions were assayed and compared, respectively, for the uncoated and chitosan-coated nanoliposomes prepared by the two introduced methods.
The prepared chitosan-lipid hybrid structures, with nanometric size, have shown high indomethacin loading (about 10%) and drug encapsulation efficiency up to 99%. TEM investigation has highlighted that the developed novel simil-microfluidic method is able to put a polymeric layer, surrounding indomethacin loaded nanoliposomes, thicker and smoother than that achievable by the drop-wise method, improving their storage stability. Finally, double pH tests have confirmed that the chitosan-lipid hybrid nanostructures have a gastro retentive behavior in simulated gastric and intestinal fluids thus can be used as delivery systems for the oral-controlled release of indomethacin.
Based on the present results, the simil-microfluidic method, working with large volumes, in a rapid manner, without the use of drastic conditions and with a precise control over the covering process, seems to be the most promising method for the production of suitable indomethacin delivery system, with a great potential in industrial manufacturing.2017
Dalmoro, Annalisa; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela
Encapsulation of Active Molecules in Microparticles Based on Natural Polysaccharides Journal Article
Natural Product Communications, 12 (6), pp. 863-866, 2017, ISSN: 1934-578X.
@article{NPC01,
title = {Encapsulation of Active Molecules in Microparticles Based on Natural Polysaccharides},
author = {Annalisa Dalmoro and Sara Cascone and Gaetano Lamberti and Anna Angela Barba},
url = {http://www.naturalproduct.us/index.asp
https://www.gruppotpp.it/wp-content/uploads/2017/06/Dalmoro-et-al-NPC-126-863-866-2017-Abstract-1.pdf},
issn = {1934-578X},
year = {2017},
date = {2017-07-31},
journal = {Natural Product Communications},
volume = {12},
number = {6},
pages = {863-866},
abstract = {This mini-review is focused on an engineering approach to produce polysaccharides-based microparticles for nutraceutical and pharmaceutical purposes. A brief introduction about the fundamental properties of polysaccharides and their use as microsystems in food, cosmetics, and pharmaceutics, and a summary of the most important methods of preparation are described. Then, a novel method based on the ultrasonic atomization of solutions of the two most used polysaccharides, alginate and chitosan, followed by ionotropic gelation to produce enteric microsystems for oral administration and, in particular, the basic mechanisms of the encapsulation of molecules with different size and hydrophilicity, are investigated. This mini-review will show therefore the pathway to correctly design a polysaccharide microcarrier for the encapsulation of active molecules with different properties: from the choice of materials features, to the selection and the optimization of production methods with the aim to reduce costs and energy (ionotropic gelation coupled to ultrasonic atomization), to the control of the final carrier size (by purposely developed predictive models), at last to the optimization of encapsulation properties (predicting by model the drug leakage and providing different solutions to avoid it).},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
This mini-review is focused on an engineering approach to produce polysaccharides-based microparticles for nutraceutical and pharmaceutical purposes. A brief introduction about the fundamental properties of polysaccharides and their use as microsystems in food, cosmetics, and pharmaceutics, and a summary of the most important methods of preparation are described. Then, a novel method based on the ultrasonic atomization of solutions of the two most used polysaccharides, alginate and chitosan, followed by ionotropic gelation to produce enteric microsystems for oral administration and, in particular, the basic mechanisms of the encapsulation of molecules with different size and hydrophilicity, are investigated. This mini-review will show therefore the pathway to correctly design a polysaccharide microcarrier for the encapsulation of active molecules with different properties: from the choice of materials features, to the selection and the optimization of production methods with the aim to reduce costs and energy (ionotropic gelation coupled to ultrasonic atomization), to the control of the final carrier size (by purposely developed predictive models), at last to the optimization of encapsulation properties (predicting by model the drug leakage and providing different solutions to avoid it).Barba, Anna Angela; Cascone, Sara; Caccavo, Diego; Lamberti, Gaetano; Chiarappa, Gianluca; Abrami, Michela; Grassi, Gabriele; Grassi, Mario; Tomaiuolo, Giovanna; Guido, Stefano; Brucato, Valerio; Carfì Pavia, Francesco ; Ghersi, Giulio; La Carrubba, Vincenzo ; Abbiati, Roberto Andrea; Manca, Davide
Engineering approaches in siRNA delivery Journal Article
International Journal of Pharmaceutics, 525 (2), pp. 343–358, 2017.
@article{Barba2017,
title = {Engineering approaches in siRNA delivery},
author = {Anna Angela Barba and Sara Cascone and Diego Caccavo and Gaetano Lamberti and Gianluca Chiarappa and Michela Abrami and Gabriele Grassi and Mario Grassi and Giovanna Tomaiuolo and Stefano Guido and Valerio Brucato and Francesco {Carf\`{i} Pavia} and Giulio Ghersi and Vincenzo {La Carrubba} and Roberto Andrea Abbiati and Davide Manca},
url = {http://www.sciencedirect.com/science/article/pii/S0378517317301138},
doi = {10.1016/j.ijpharm.2017.02.032},
year = {2017},
date = {2017-06-20},
journal = {International Journal of Pharmaceutics},
volume = {525},
number = {2},
pages = {343\textendash358},
abstract = {siRNAs are very potent drug molecules, able to silence genes involved in pathologies development. siRNAs have virtually an unlimited therapeutic potential, particularly for the treatment of inflammatory diseases. However, their use in clinical practice is limited because of their unfavorable properties to interact and not to degrade in physiological environments. In particular they are large macromolecules, negatively charged, which undergo rapid degradation by plasmatic enzymes, are subject to fast renal clearance/hepatic sequestration, and can hardly cross cellular membranes. These aspects seriously impair siRNAs as therapeutics. As in all the other fields of science, siRNAs management can be advantaged by physical-mathematical descriptions (modeling) in order to clarify the involved phenomena from the preparative step of dosage systems to the description of drug-body interactions, which allows improving the design of delivery systems/processes/therapies. This review analyzes a few mathematical modeling approaches currently adopted to describe the siRNAs delivery, the main procedures in siRNAs vectors’ production processes and siRNAs vectors’ release from hydrogels, and the modeling of pharmacokinetics of siRNAs vectors. Furthermore, the use of physical models to study the siRNAs vectors’ fate in blood stream and in the tissues is presented. The general view depicts a framework maybe not yet usable in therapeutics, but with promising possibilities for forthcoming applications.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
siRNAs are very potent drug molecules, able to silence genes involved in pathologies development. siRNAs have virtually an unlimited therapeutic potential, particularly for the treatment of inflammatory diseases. However, their use in clinical practice is limited because of their unfavorable properties to interact and not to degrade in physiological environments. In particular they are large macromolecules, negatively charged, which undergo rapid degradation by plasmatic enzymes, are subject to fast renal clearance/hepatic sequestration, and can hardly cross cellular membranes. These aspects seriously impair siRNAs as therapeutics. As in all the other fields of science, siRNAs management can be advantaged by physical-mathematical descriptions (modeling) in order to clarify the involved phenomena from the preparative step of dosage systems to the description of drug-body interactions, which allows improving the design of delivery systems/processes/therapies. This review analyzes a few mathematical modeling approaches currently adopted to describe the siRNAs delivery, the main procedures in siRNAs vectors’ production processes and siRNAs vectors’ release from hydrogels, and the modeling of pharmacokinetics of siRNAs vectors. Furthermore, the use of physical models to study the siRNAs vectors’ fate in blood stream and in the tissues is presented. The general view depicts a framework maybe not yet usable in therapeutics, but with promising possibilities for forthcoming applications.Bochicchio, Sabrina; Dapas, Barbara; Russo, Ilaria; Ciacci, Carolina; Piazza, Ornella; De Smedt, Stefan ; Pottie, Eline; Barba, Anna Angela; Grassi, Gabriele
In vitro and ex vivo delivery of tailored siRNA-nanoliposomes for E2F1 silencing as a potential therapy for colorectal cancer Journal Article
International Journal of Pharmaceutics, 525 (2), pp. 377–387, 2017.
@article{Bochicchio2017,
title = {In vitro and ex vivo delivery of tailored siRNA-nanoliposomes for E2F1 silencing as a potential therapy for colorectal cancer},
author = {Sabrina Bochicchio and Barbara Dapas and Ilaria Russo and Carolina Ciacci and Ornella Piazza and Stefan {De Smedt} and Eline Pottie and Anna Angela Barba and Gabriele Grassi},
url = {http://www.sciencedirect.com/science/article/pii/S0378517317301011},
doi = {10.1016/j.ijpharm.2017.02.020},
year = {2017},
date = {2017-06-20},
journal = {International Journal of Pharmaceutics},
volume = {525},
number = {2},
pages = {377\textendash387},
abstract = {Tailored developed nanoliposomes loaded with a siRNA against the transcription factor E2F1 (siE2F1), were produced and delivered to human colorectal adenocarcinoma cell lines and to intestinal human biopsies. siE2F1 loaded nanoliposomes were produced through a dedicated ultrasound assisted technique producing particles with about 40 nm size (Small Unilamellar Vesicles, SUVs) and 100% siRNA encapsulation efficiency. Compared to other production methods, the one proposed here can easily produce particles in the nanometric scale by suitable ultrasonic duty cycle treatments. Furthermore, SUVs have a high degree of size homogeneity, a relevant feature for uniform delivery behaviour.
siE2F1-loaded SUVs demonstrated a very low cytotoxicity in cells when compared to a commercial transfection agent. Moreover, SUVs loaded with siE2F1 were effective in the down regulation of the target in cultured colon carcinoma cells and in the consequent reduction of cell growth. Finally, a remarkable uptake and target silencing efficiencies were observed in cultured human biopsy of colonic mucosa. In conclusion, whereas further studies in more complex models are required, the siE2F1-SUVs generated have the potential to contribute to the development of novel effective inflammatory bowel diseases-associated colorectal cancer therapies for a future personalized medicine.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Tailored developed nanoliposomes loaded with a siRNA against the transcription factor E2F1 (siE2F1), were produced and delivered to human colorectal adenocarcinoma cell lines and to intestinal human biopsies. siE2F1 loaded nanoliposomes were produced through a dedicated ultrasound assisted technique producing particles with about 40 nm size (Small Unilamellar Vesicles, SUVs) and 100% siRNA encapsulation efficiency. Compared to other production methods, the one proposed here can easily produce particles in the nanometric scale by suitable ultrasonic duty cycle treatments. Furthermore, SUVs have a high degree of size homogeneity, a relevant feature for uniform delivery behaviour.
siE2F1-loaded SUVs demonstrated a very low cytotoxicity in cells when compared to a commercial transfection agent. Moreover, SUVs loaded with siE2F1 were effective in the down regulation of the target in cultured colon carcinoma cells and in the consequent reduction of cell growth. Finally, a remarkable uptake and target silencing efficiencies were observed in cultured human biopsy of colonic mucosa. In conclusion, whereas further studies in more complex models are required, the siE2F1-SUVs generated have the potential to contribute to the development of novel effective inflammatory bowel diseases-associated colorectal cancer therapies for a future personalized medicine.Lamberti, Gaetano
Delivery of siRNAs Journal Article
International Journal of Pharmaceutics, 525 (2), pp. 291–292, 2017.
@article{Lamberti2017,
title = {Delivery of siRNAs},
author = {Gaetano Lamberti},
url = {http://www.sciencedirect.com/science/article/pii/S0378517317304118},
doi = {10.1016/j.ijpharm.2017.05.010},
year = {2017},
date = {2017-06-20},
journal = {International Journal of Pharmaceutics},
volume = {525},
number = {2},
pages = {291\textendash292},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Dalmoro, Annalisa; Sitenkov, Alexander Y; Cascone, Sara; Lamberti, Gaetano; Barba, Anna Angela; Moustafine, Rouslan I
Hydrophilic drug encapsulation in shell-core microcarriers by two stage polyelectrolyte complexation method Journal Article
International Journal of Pharmaceutics, 518 (1-2), pp. 50–58, 2017.
@article{Dalmoro2017,
title = {Hydrophilic drug encapsulation in shell-core microcarriers by two stage polyelectrolyte complexation method},
author = {Annalisa Dalmoro and Alexander Y. Sitenkov and Sara Cascone and Gaetano Lamberti and Anna Angela Barba and Rouslan I. Moustafine},
url = {http://www.sciencedirect.com/science/article/pii/S037851731631198X},
doi = {10.1016/j.ijpharm.2016.12.056},
year = {2017},
date = {2017-02-25},
journal = {International Journal of Pharmaceutics},
volume = {518},
number = {1-2},
pages = {50\textendash58},
abstract = {In this study a protocol exploiting the combination of the ultrasonic atomization and the complexation between polyelectrolytes was developed to efficiently encapsulate a hydrophilic chemotherapeutic agent essentially used in the treatment of colon cancer, 5-fluorouracil, in enteric shell-core alginate-based microcarriers. The atomization assisted by ultrasound allowed to obtain small droplets by supplying low energy and avoiding drug degradation. In particular microcarriers were produced in a home-made apparatus where both the core (composed of alginate, drug, and Pluronic F127) and shell (composed of only alginate) feed were separately sent to the coaxial ultrasonic atomizer where they were nebulized and placed in contact with the complexation bulk. With the aim to obtain microstructured particles of alginate encapsulating 5-fluorouracil, different formulations of the first complexation bulk were tested; at last an emulsion made of a calcium chloride aqueous solution and dichloromethane allowed to reach an encapsulation efficiency of about 50%. This result can be considered very interesting considering that in literature similar techniques gave 5-fluorouracil encapsulation efficiencies of about 10%.
Since a single complexation stage was not able to assure microcarriers gastroresistance, the formulation of a second complexation bulk was evaluated. The solution of cationic and pH-insoluble Eudragit® RS 100 in dichloromethane was chosen as bulk of second-stage complexation obtaining good enteric properties of shell-core microcarriers, i.e. a 5-FU cumulative release at pH 1 (simulating gastric pH) lower than 35%. The formation of interpolyelectrolyte complex (IPEC) between countercharged polymers and the chemical stability of 5-FU in microcarriers were confirmed by FTIR analysis, the presence of an amorphous dispersion of 5-FU in prepared microparticles was also confirmed by DSC. Finally, shell-core enteric coated microcarriers encapsulating 5-fluorouracil were used to prepare tablets, which can be potentially used as oral administration dosage systems for their 5-fluorouracil slower release.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In this study a protocol exploiting the combination of the ultrasonic atomization and the complexation between polyelectrolytes was developed to efficiently encapsulate a hydrophilic chemotherapeutic agent essentially used in the treatment of colon cancer, 5-fluorouracil, in enteric shell-core alginate-based microcarriers. The atomization assisted by ultrasound allowed to obtain small droplets by supplying low energy and avoiding drug degradation. In particular microcarriers were produced in a home-made apparatus where both the core (composed of alginate, drug, and Pluronic F127) and shell (composed of only alginate) feed were separately sent to the coaxial ultrasonic atomizer where they were nebulized and placed in contact with the complexation bulk. With the aim to obtain microstructured particles of alginate encapsulating 5-fluorouracil, different formulations of the first complexation bulk were tested; at last an emulsion made of a calcium chloride aqueous solution and dichloromethane allowed to reach an encapsulation efficiency of about 50%. This result can be considered very interesting considering that in literature similar techniques gave 5-fluorouracil encapsulation efficiencies of about 10%.
Since a single complexation stage was not able to assure microcarriers gastroresistance, the formulation of a second complexation bulk was evaluated. The solution of cationic and pH-insoluble Eudragit® RS 100 in dichloromethane was chosen as bulk of second-stage complexation obtaining good enteric properties of shell-core microcarriers, i.e. a 5-FU cumulative release at pH 1 (simulating gastric pH) lower than 35%. The formation of interpolyelectrolyte complex (IPEC) between countercharged polymers and the chemical stability of 5-FU in microcarriers were confirmed by FTIR analysis, the presence of an amorphous dispersion of 5-FU in prepared microparticles was also confirmed by DSC. Finally, shell-core enteric coated microcarriers encapsulating 5-fluorouracil were used to prepare tablets, which can be potentially used as oral administration dosage systems for their 5-fluorouracil slower release.Barba, Anna Angela; Grassi, Gabriele; Grassi, Mario; Lamberti, Gaetano
New Trends in Gene Therapy: Multidisciplinary Approaches to siRNAs Controlled Delivery Journal Article
Current Drug Delivery, 14 (2), pp. 156-157, 2017.
@article{Barba2017b,
title = {New Trends in Gene Therapy: Multidisciplinary Approaches to siRNAs Controlled Delivery},
author = {Anna Angela Barba and Gabriele Grassi and Mario Grassi and Gaetano Lamberti},
url = {https://www.gruppotpp.it/wp-content/uploads/2017/03/01.-Barba-et-al-CDD-142-156-157-2017.pdf
http://www.eurekaselect.com/149727},
doi = {10.2174/156720181402170202202808},
year = {2017},
date = {2017-02-09},
journal = {Current Drug Delivery},
volume = {14},
number = {2},
pages = {156-157},
abstract = {Nucleic acid based drugs (NABDs), powerful in principle, can be of great importance for health care applications if and
only if effective delivery systems are available. Among NABDs, small interfering RNAs (siRNAs) show revolutionary potentiality
due to the ability to silencing the expression of gene-causing diseases. Thus, siRNA drugs have huge therapeutic potentials,
even in the treatment of life threatening diseases. However, the use of siRNAs is limited because of some inconveniences:
they are large macromolecules, negatively charged, undergo rapid degradation by plasma enzymes, are subjected to fast renal
clearance/hepatic sequestration and can hardly cross cellular membranes. These aspects seriously impair siRNAs usability as
therapeutics. To overcome these obstacles, the scientific problem has to be faced out through a multidisciplinary approach, integrating
all relevant and necessary expertise. In this Full-Thematic Issue of the Current Drug Delivery, the development of
siRNAs delivery approaches is described from different points of view by several research groups, which have been jointly
working on the subject in the last years.
The Thematic Issue starts with the paper by Chiarappa et al., devoted to describe the potentiality of the Chemical Engineering
expertise in the “Bio world” through reminding the foundation of Biological Engineering (BE) that develops, with its current
and multidisciplinary approaches, winning strategies in modern research. The concepts of unit operations and transport
phenomena, with which chemical engineers are confident, are applied to the description of the biomedical/pharmaceutical
world and to the study of siRNAs delivery, in order to get a better understanding and description of how biological systems
work.
The engineering approach to siRNA delivery is, then, reported analyzing two topics. In particular, the paper by Caccavo
et al. deals with the modeling of hydrogel based drug delivery systems, materials widely used in controlled drug delivery,
which could be adopted also for siRNAs delivery. Abbiati and Manca report the use of a physiologically-based pharmacokinetic
model, useful in order to assess the fate of drugs, including siRNAs, once administered. The novel preparative methods to
be used in siRNAs delivery are the subjects of the paper by Bochicchio et al., focusing on both the lipid-based and the polymerbased
carriers. More specifically, Dalmoro et al. discuss the use of injectable chitosan/β-glycerophosphate systems, whereas
Cavallaro et al. report the uses of polycation-based smart carriers for siRNAs delivery. Advanced testing methods for the study
of drug delivery systems and the interactions between delivery systems and living systems are discussed in the paper by
D’Apolito et al. and Carf\`{i}-Pavia et al. D’Apolito et al. focus on the effect of liposomal carriers in microcirculation; Carf\`{i}-Pavia
et al. concentrate the attention on a novel bioreactor able to mimic the vascular behavior for in-vitro tests of drug delivery. Last
but not the least, the medical applications of novel delivery systems and siRNAs are discussed in the paper by Piazza et al.,
focusing on the delivery of siRNAs by liposomes in order to silence cycline D1 in ex-vivo human tissues. Moreover, the paper
by Di Gioia et al., deals with the siRNAs’ based therapies against inflammatory respiratory diseases, while the paper by Farra
et al., discusses the role of the transcription factor E2F1 in hepatocellular carcinoma and the opportunity of its silencing by siRNAs.
In conclusion, the papers presented strongly indicate that only a multidisciplinary approach can successfully overcome the
still existing limitation in the use of siRNAs, molecules with an extraordinary therapeutic potential.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Nucleic acid based drugs (NABDs), powerful in principle, can be of great importance for health care applications if and
only if effective delivery systems are available. Among NABDs, small interfering RNAs (siRNAs) show revolutionary potentiality
due to the ability to silencing the expression of gene-causing diseases. Thus, siRNA drugs have huge therapeutic potentials,
even in the treatment of life threatening diseases. However, the use of siRNAs is limited because of some inconveniences:
they are large macromolecules, negatively charged, undergo rapid degradation by plasma enzymes, are subjected to fast renal
clearance/hepatic sequestration and can hardly cross cellular membranes. These aspects seriously impair siRNAs usability as
therapeutics. To overcome these obstacles, the scientific problem has to be faced out through a multidisciplinary approach, integrating
all relevant and necessary expertise. In this Full-Thematic Issue of the Current Drug Delivery, the development of
siRNAs delivery approaches is described from different points of view by several research groups, which have been jointly
working on the subject in the last years.
The Thematic Issue starts with the paper by Chiarappa et al., devoted to describe the potentiality of the Chemical Engineering
expertise in the “Bio world” through reminding the foundation of Biological Engineering (BE) that develops, with its current
and multidisciplinary approaches, winning strategies in modern research. The concepts of unit operations and transport
phenomena, with which chemical engineers are confident, are applied to the description of the biomedical/pharmaceutical
world and to the study of siRNAs delivery, in order to get a better understanding and description of how biological systems
work.
The engineering approach to siRNA delivery is, then, reported analyzing two topics. In particular, the paper by Caccavo
et al. deals with the modeling of hydrogel based drug delivery systems, materials widely used in controlled drug delivery,
which could be adopted also for siRNAs delivery. Abbiati and Manca report the use of a physiologically-based pharmacokinetic
model, useful in order to assess the fate of drugs, including siRNAs, once administered. The novel preparative methods to
be used in siRNAs delivery are the subjects of the paper by Bochicchio et al., focusing on both the lipid-based and the polymerbased
carriers. More specifically, Dalmoro et al. discuss the use of injectable chitosan/β-glycerophosphate systems, whereas
Cavallaro et al. report the uses of polycation-based smart carriers for siRNAs delivery. Advanced testing methods for the study
of drug delivery systems and the interactions between delivery systems and living systems are discussed in the paper by
D’Apolito et al. and Carfì-Pavia et al. D’Apolito et al. focus on the effect of liposomal carriers in microcirculation; Carfì-Pavia
et al. concentrate the attention on a novel bioreactor able to mimic the vascular behavior for in-vitro tests of drug delivery. Last
but not the least, the medical applications of novel delivery systems and siRNAs are discussed in the paper by Piazza et al.,
focusing on the delivery of siRNAs by liposomes in order to silence cycline D1 in ex-vivo human tissues. Moreover, the paper
by Di Gioia et al., deals with the siRNAs’ based therapies against inflammatory respiratory diseases, while the paper by Farra
et al., discusses the role of the transcription factor E2F1 in hepatocellular carcinoma and the opportunity of its silencing by siRNAs.
In conclusion, the papers presented strongly indicate that only a multidisciplinary approach can successfully overcome the
still existing limitation in the use of siRNAs, molecules with an extraordinary therapeutic potential.Bochicchio, Sabrina; Dalmoro, Annalisa; Barba, Anna Angela; D'Amore, Matteo; Lamberti, Gaetano
New preparative approaches for micro and nano drug delivery carriers Journal Article
Current Drug Delivery, 14 (2), pp. 203 - 215, 2017.
@article{Bochicchio2016b,
title = {New preparative approaches for micro and nano drug delivery carriers},
author = {Sabrina Bochicchio and Annalisa Dalmoro and Anna Angela Barba and Matteo D'Amore and Gaetano Lamberti},
url = {https://www.gruppotpp.it/wp-content/uploads/2017/03/05.-Bochicchio-et-al-CDD-142-203-215-2017.pdf
http://benthamscience.com/journals/current-drug-delivery/volume/14/issue/2/page/203/},
doi = {10.2174/1567201813666160628093724},
year = {2017},
date = {2017-02-08},
issuetitle = {NEW TRENDS IN GENE THERAPY: MULTIDISCIPLINARY APPROACHES TO SIRNAS CONTROLLED DELIVERY},
journal = {Current Drug Delivery},
volume = {14},
number = {2},
pages = {203 - 215},
abstract = {The full success of pharmacological therapies is strongly depending from the use of suitable, efficient and smart drug delivery systems (DDSs). Thus DDSs development is one of the main challenges in pharmaceutical industry both to achieve tailored carrier systems based on drug features and to promote manufacturing innovations to reduce energetic resources, emissions, wastes and risks. Main functions of an ideal DDS are: to protect loaded active molecules from degradation in physiological environments; to deliver them in a controlled manner and towards a specific organ or tissue, to allow the maintenance of the drug level in the body within therapeutic window. Smart features, such as those able to induce active molecule release upon the occurrence of specific physiological stimuli, are also desirable. Under the manufacturing point of view, the current industrial scenery is obliged to respond to the increasing market requirements and to the mandatory rules in sustainable productions such as raw material and energy savings.
In this work a general framework on drug delivery systems preparation techniques is presented. In particular two sections on innovation in preparative approaches carried out are detailed. These latter involve the use of microwave and ultrasonic energy applied in the production of polymeric and lipidic delivery systems on micro- and nanometric scale. The novelties of these preparative approaches are emphasized and examples of developed drug delivery carriers, loaded with vitamins and drug mimicking siRNA, are shown.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The full success of pharmacological therapies is strongly depending from the use of suitable, efficient and smart drug delivery systems (DDSs). Thus DDSs development is one of the main challenges in pharmaceutical industry both to achieve tailored carrier systems based on drug features and to promote manufacturing innovations to reduce energetic resources, emissions, wastes and risks. Main functions of an ideal DDS are: to protect loaded active molecules from degradation in physiological environments; to deliver them in a controlled manner and towards a specific organ or tissue, to allow the maintenance of the drug level in the body within therapeutic window. Smart features, such as those able to induce active molecule release upon the occurrence of specific physiological stimuli, are also desirable. Under the manufacturing point of view, the current industrial scenery is obliged to respond to the increasing market requirements and to the mandatory rules in sustainable productions such as raw material and energy savings.
In this work a general framework on drug delivery systems preparation techniques is presented. In particular two sections on innovation in preparative approaches carried out are detailed. These latter involve the use of microwave and ultrasonic energy applied in the production of polymeric and lipidic delivery systems on micro- and nanometric scale. The novelties of these preparative approaches are emphasized and examples of developed drug delivery carriers, loaded with vitamins and drug mimicking siRNA, are shown.2016
Bochicchio, Sabrina; Barba, Anna Angela; Grassi, Gabriele; Lamberti, Gaetano
Vitamin delivery: Carriers based on nanoliposomes produced via ultrasonic irradiation Journal Article
LWT - Food Science and Technology, 69 , pp. 9-16, 2016.
@article{Bochicchio2016,
title = {Vitamin delivery: Carriers based on nanoliposomes produced via ultrasonic irradiation},
author = {Sabrina Bochicchio and Anna Angela Barba and Gabriele Grassi and Gaetano Lamberti},
url = {http://www.sciencedirect.com/science/article/pii/S0023643816300251},
doi = {10.1016/j.lwt.2016.01.025},
year = {2016},
date = {2016-06-01},
journal = {LWT - Food Science and Technology},
volume = {69},
pages = {9-16},
abstract = {In recent years much attention has been focused on using lipid carriers as potential delivery systems for bioactive molecules due to their favorable properties such as high biocompatibility, size and composition versatility. In this paper formulation, preparation and characterization of liposomes, a class of powerfully versatile lipidic carriers, produced by means of an innovative ultrasound-assisted approach based on the thin-film hydration method, are presented and discussed. The main aim of this study is to obtain nanostructures (Small Unilamellar Vesicles, SUVs), less than 100 nm in size, loaded with different vitamins (B12, tocopherol and ergocalciferol), starting from lipidic microstructures (Multilamellar Large Vesicles, MLVs). Suitable formulations, sonication protocols and nanoliposomes were pointed out. SUVs with diameter size ranging from 40 nm to 51 nm were achieved starting from MLVs with a diameter range of 2.9 - 5.7 μm. Starting from MLVs with higher encapsulation efficiency for all kind of vitamins, SUVs with an encapsulation efficiency of 56% for vitamin B12, 76% for α-tocopherol and 57% for ergocalciferol were obtained. Stability tests have shown that the used lipid composition allows to keep intact the nanovesicles and their content for more than 10 days if incubated at simulated extracellular environment conditions.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In recent years much attention has been focused on using lipid carriers as potential delivery systems for bioactive molecules due to their favorable properties such as high biocompatibility, size and composition versatility. In this paper formulation, preparation and characterization of liposomes, a class of powerfully versatile lipidic carriers, produced by means of an innovative ultrasound-assisted approach based on the thin-film hydration method, are presented and discussed. The main aim of this study is to obtain nanostructures (Small Unilamellar Vesicles, SUVs), less than 100 nm in size, loaded with different vitamins (B12, tocopherol and ergocalciferol), starting from lipidic microstructures (Multilamellar Large Vesicles, MLVs). Suitable formulations, sonication protocols and nanoliposomes were pointed out. SUVs with diameter size ranging from 40 nm to 51 nm were achieved starting from MLVs with a diameter range of 2.9 - 5.7 μm. Starting from MLVs with higher encapsulation efficiency for all kind of vitamins, SUVs with an encapsulation efficiency of 56% for vitamin B12, 76% for α-tocopherol and 57% for ergocalciferol were obtained. Stability tests have shown that the used lipid composition allows to keep intact the nanovesicles and their content for more than 10 days if incubated at simulated extracellular environment conditions.Dalmoro, Annalisa; Sitenkov, Alexander Y; Lamberti, Gaetano; Barba, Anna Angela; Moustafine, Rouslan I
Ultrasonic atomization and polyelectrolyte complexation to produce gastroresistant shell–core microparticles Journal Article
Journal of Applied Polymer Science, 133 (42976), 2016.
@article{Dalmoro2016,
title = {Ultrasonic atomization and polyelectrolyte complexation to produce gastroresistant shell\textendashcore microparticles},
author = {Annalisa Dalmoro and Alexander Y. Sitenkov and Gaetano Lamberti and Anna Angela Barba and Rouslan I. Moustafine},
url = {http://onlinelibrary.wiley.com/doi/10.1002/app.42976/abstract},
doi = {10.1002/app.42976},
year = {2016},
date = {2016-02-10},
journal = {Journal of Applied Polymer Science},
volume = {133},
number = {42976},
abstract = {In this study ultrasound-assisted atomization technique was combined with two-stages polyelectrolyte complexation to produce enteric shell\textendashcore microparticles encapsulating a non-steroidal, anti-inflammatory gastrolesive active ingredient indomethacin. In particular, a solution of the anionic biopolymer alginate, containing indomethacin, was sprayed in fine droplets which were complexed with a cationic (meth)acrylate copolymer, Eudragit® E 100, which, in turn, was complexed by the anionic copolymer Eudragit® L30D-55. The first complexation stage was applied to achieve a high drug encapsulation efficiency; the second one to assure good gastroresistance feature. The novel protocol has been found more effective in terms of loading, encapsulation efficiency, and enteric properties during in vitro release tests, than conventional procedures which involved alginate cross-linking by charged ions. Furthermore ultrasonic atomization\textendashpolyelectrolytes complexation preparation approach was performed using mild conditions, aqueous solutions, in the absence of organic solvents and chemical cross-linkers. },
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In this study ultrasound-assisted atomization technique was combined with two-stages polyelectrolyte complexation to produce enteric shell–core microparticles encapsulating a non-steroidal, anti-inflammatory gastrolesive active ingredient indomethacin. In particular, a solution of the anionic biopolymer alginate, containing indomethacin, was sprayed in fine droplets which were complexed with a cationic (meth)acrylate copolymer, Eudragit® E 100, which, in turn, was complexed by the anionic copolymer Eudragit® L30D-55. The first complexation stage was applied to achieve a high drug encapsulation efficiency; the second one to assure good gastroresistance feature. The novel protocol has been found more effective in terms of loading, encapsulation efficiency, and enteric properties during in vitro release tests, than conventional procedures which involved alginate cross-linking by charged ions. Furthermore ultrasonic atomization–polyelectrolytes complexation preparation approach was performed using mild conditions, aqueous solutions, in the absence of organic solvents and chemical cross-linkers.2015
Cavallaro, Gennara; Craparo, Emanuela Fabiola; Sardo, Carla; Lamberti, Gaetano; Barba, Anna Angela; Dalmoro, Annalisa
PHEA-PLA biocompatible nanoparticles by technique of solvent evaporation from multiple emulsions. Journal Article
International journal of pharmaceutics, 495 (2), pp. 719-727, 2015, ISSN: 1873-3476.
@article{Cavallaro2015,
title = {PHEA-PLA biocompatible nanoparticles by technique of solvent evaporation from multiple emulsions.},
author = { Gennara Cavallaro and Emanuela Fabiola Craparo and Carla Sardo and Gaetano Lamberti and Anna Angela Barba and Annalisa Dalmoro},
url = {http://www.sciencedirect.com/science/article/pii/S0378517315302519},
doi = {10.1016/j.ijpharm.2015.09.050},
issn = {1873-3476},
year = {2015},
date = {2015-09-01},
journal = {International journal of pharmaceutics},
volume = {495},
number = {2},
pages = {719-727},
abstract = {Nanocarriers of amphiphilic polymeric materials represent versatile delivery systems for poorly water soluble drugs. In this work the technique of solvent evaporation from multiple emulsions was applied to produce nanovectors based on new amphiphilic copolymer, the $alpha$,$beta$-poly(N-2-hydroxyethyl)-DL-aspartamide - polylactic acid (PHEA - PLA), purposely synthesized to be used in the controlled release of active molecules poorly soluble in water. To this aim an amphiphilic derivative of PHEA, a hydrophilic polymer, was synthesized by derivatization of the polymeric backbone with hydrophobic grafts of polylactic acid (PLA). The achieved copolymer was thus used to produce nanoparticles loaded with $alpha$ tocopherol (vitamin E) adopted as lipophilic model molecule. Applying a protocol based on solvent evaporation from multiple emulsions assisted by ultrasonic energy and optimizing the emulsification process (solvent selection/separation stages), PHEA-PLA nanostructured particles with total $alpha$ tocopherol entrapment efficiency (100%), were obtained. The drug release is expected to take place in lower times with respect to PLA due to the presence of the hydrophilic PHEA, therefore the produced nanoparticles can be used for semi- long term release drug delivery systems.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Nanocarriers of amphiphilic polymeric materials represent versatile delivery systems for poorly water soluble drugs. In this work the technique of solvent evaporation from multiple emulsions was applied to produce nanovectors based on new amphiphilic copolymer, the $alpha$,$beta$-poly(N-2-hydroxyethyl)-DL-aspartamide - polylactic acid (PHEA - PLA), purposely synthesized to be used in the controlled release of active molecules poorly soluble in water. To this aim an amphiphilic derivative of PHEA, a hydrophilic polymer, was synthesized by derivatization of the polymeric backbone with hydrophobic grafts of polylactic acid (PLA). The achieved copolymer was thus used to produce nanoparticles loaded with $alpha$ tocopherol (vitamin E) adopted as lipophilic model molecule. Applying a protocol based on solvent evaporation from multiple emulsions assisted by ultrasonic energy and optimizing the emulsification process (solvent selection/separation stages), PHEA-PLA nanostructured particles with total $alpha$ tocopherol entrapment efficiency (100%), were obtained. The drug release is expected to take place in lower times with respect to PLA due to the presence of the hydrophilic PHEA, therefore the produced nanoparticles can be used for semi- long term release drug delivery systems.Barba, Anna Angela; Lamberti, Gaetano; Sardo, Carla; Dapas, Barbara; Abrami, Michela; Grassi, Mario; Farra, Rossella; Tonon, F; Forte, Giancarlo; Musiani, F; Licciardi, M; Pozzato, G; Zanconati, F; Scaggiante, Bruna; Grassi, Gabriele; Cavallaro, Gennara
Novel Lipid and Polymeric Materials As Delivery Systems for Nucleic Acid Based Drugs. Journal Article
Current drug metabolism, 16 (6), pp. 427-452, 2015, ISSN: 1389-2002.
@article{Barba2015,
title = {Novel Lipid and Polymeric Materials As Delivery Systems for Nucleic Acid Based Drugs.},
author = { Anna Angela Barba and Gaetano Lamberti and Carla Sardo and Barbara Dapas and Michela Abrami and Mario Grassi and Rossella Farra and F Tonon and Giancarlo Forte and F Musiani and M Licciardi and G Pozzato and F Zanconati and Bruna Scaggiante and Gabriele Grassi and Gennara Cavallaro},
url = {http://benthamscience.com/journals/current-drug-metabolism/article/133927/},
doi = {10.2174/1389200216666150812142557},
issn = {1389-2002},
year = {2015},
date = {2015-01-01},
journal = {Current drug metabolism},
volume = {16},
number = {6},
pages = {427-452},
abstract = {Nucleic acid based drugs (NADBs) are short DNA/RNA molecules that include among others, antisense oligonucleotides, aptamers, small interfering RNAs and micro-interfering RNAs. Despite the different mechanisms of actions, NABDs have the ability to combat the effects of pathological gene expression in many experimental systems. Thus, nowadays, NABDs are considered to have a great therapeutic potential, possibly superior to that of available drugs. Unfortunately, however, the lack of effective delivery systems limits the practical use of NABDs. Due to their hydrophilic nature, NABDs cannot efficiently cross cellular membrane; in addition, they are subjected to fast degradation by cellular and extracellular nucleases. Together these aspects make the delivery of NABDs as naked molecules almost un-effective. To optimize NABD delivery, several solutions have been investigated. From the first attempts described in the beginning of the 1980s, a burst in the number of published papers occurred in the beginning of 1990s reaching a peak in 2012-13. The extensive amount of work performed so far clearly witnesses the interest of the scientific community in this topic. In the present review, we will concentrate on the description of the most interesting advances in the field. Particular emphasis will be put on polymeric and lipid materials used alone or in combination with a promising delivery strategy based on the use of carbon nanotubes. The data presented suggest that, although further improvements are required, we are not far from the identification of effective delivery systems for NABDs thus making the clinical use of these molecules closer to reality.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Nucleic acid based drugs (NADBs) are short DNA/RNA molecules that include among others, antisense oligonucleotides, aptamers, small interfering RNAs and micro-interfering RNAs. Despite the different mechanisms of actions, NABDs have the ability to combat the effects of pathological gene expression in many experimental systems. Thus, nowadays, NABDs are considered to have a great therapeutic potential, possibly superior to that of available drugs. Unfortunately, however, the lack of effective delivery systems limits the practical use of NABDs. Due to their hydrophilic nature, NABDs cannot efficiently cross cellular membrane; in addition, they are subjected to fast degradation by cellular and extracellular nucleases. Together these aspects make the delivery of NABDs as naked molecules almost un-effective. To optimize NABD delivery, several solutions have been investigated. From the first attempts described in the beginning of the 1980s, a burst in the number of published papers occurred in the beginning of 1990s reaching a peak in 2012-13. The extensive amount of work performed so far clearly witnesses the interest of the scientific community in this topic. In the present review, we will concentrate on the description of the most interesting advances in the field. Particular emphasis will be put on polymeric and lipid materials used alone or in combination with a promising delivery strategy based on the use of carbon nanotubes. The data presented suggest that, although further improvements are required, we are not far from the identification of effective delivery systems for NABDs thus making the clinical use of these molecules closer to reality.Barba, Anna Angela; Dalmoro, Annalisa; D'Amore, Matteo; Lamberti, Gaetano
Liposoluble vitamin encapsulation in shell–core microparticles produced by ultrasonic atomization and microwave stabilization Journal Article
LWT - Food Science and Technology, 64 (1), pp. 149–156, 2015, ISSN: 00236438.
@article{Barba2015a,
title = {Liposoluble vitamin encapsulation in shell\textendashcore microparticles produced by ultrasonic atomization and microwave stabilization},
author = { Anna Angela Barba and Annalisa Dalmoro and Matteo D'Amore and Gaetano Lamberti},
url = {http://www.sciencedirect.com/science/article/pii/S002364381500403X},
doi = {10.1016/j.lwt.2015.05.040},
issn = {00236438},
year = {2015},
date = {2015-01-01},
journal = {LWT - Food Science and Technology},
volume = {64},
number = {1},
pages = {149--156},
abstract = {Encapsulation may protect unstable, fat soluble vitamins such as vitamin D2 (ergocalciferol). However, encapsulation by the solvent extraction and/or evaporation techniques can require toxic organic solvents, which greatly increase processing costs. The objective of this study was to evaluate the effect on ergocalciferol encapsulation by a combination of the ionic gelation method with the ultrasonic atomization and microwave drying. Optimization of manufacturing parameters included the addition of pluronic-F127 to the core solution at 1.5% w/w to increase the encapsulation efficiency to nearly 92%, greatly improving performance compared to Tween 80 at 0.5% w/w. Microwave treatment at 230 W promoted the recovery of 100% of the ergocalciferol and reduced drying times to about 30 min, while 690 W degraded 40% of the D2. In contrast, the conventional heating degraded 17% of the ergocalciferol during 12 h of processing. By all the applied methods, microparticles were produced with similar gastoresistance properties of less than 10% release at pH of 1.0, to nearly 100% release at pH of 6.8 and 240 min of dissolution. Analysis showed limited ergocalciferol degradation after 5 months of storage.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Encapsulation may protect unstable, fat soluble vitamins such as vitamin D2 (ergocalciferol). However, encapsulation by the solvent extraction and/or evaporation techniques can require toxic organic solvents, which greatly increase processing costs. The objective of this study was to evaluate the effect on ergocalciferol encapsulation by a combination of the ionic gelation method with the ultrasonic atomization and microwave drying. Optimization of manufacturing parameters included the addition of pluronic-F127 to the core solution at 1.5% w/w to increase the encapsulation efficiency to nearly 92%, greatly improving performance compared to Tween 80 at 0.5% w/w. Microwave treatment at 230 W promoted the recovery of 100% of the ergocalciferol and reduced drying times to about 30 min, while 690 W degraded 40% of the D2. In contrast, the conventional heating degraded 17% of the ergocalciferol during 12 h of processing. By all the applied methods, microparticles were produced with similar gastoresistance properties of less than 10% release at pH of 1.0, to nearly 100% release at pH of 6.8 and 240 min of dissolution. Analysis showed limited ergocalciferol degradation after 5 months of storage.2014
Dalmoro, Annalisa; Barba, Anna Angela; D'Amore, Matteo; Lamberti, Gaetano
Single-Pot Semicontinuous Bench Scale Apparatus To Produce Microparticles Journal Article
Industrial & Engineering Chemistry Research, 53 (7), pp. 2771–2780, 2014, ISSN: 0888-5885.
@article{Dalmoro2014,
title = {Single-Pot Semicontinuous Bench Scale Apparatus To Produce Microparticles},
author = { Annalisa Dalmoro and Anna Angela Barba and Matteo D'Amore and Gaetano Lamberti},
url = {http://pubs.acs.org/doi/abs/10.1021/ie403308q},
doi = {10.1021/ie403308q},
issn = {0888-5885},
year = {2014},
date = {2014-02-01},
journal = {Industrial & Engineering Chemistry Research},
volume = {53},
number = {7},
pages = {2771--2780},
publisher = {ACS Publications},
abstract = {This work presents both the design of a novel process to produce microparticles with a shell−core structure and a bench scale apparatus purposely realized. The developed process was designed to respond to mandatory needs of process intensification. It involved the coupling of two emergent technologies: atomization assisted by ultrasonic energy and microwave heating. The former was used to atomize polymeric solutions; the latter was applied to stabilize the produced droplets by drying. Both operations were performed in the same vessel with the aim to have a single-pot process chamber and were carried out by a semicontinuous procedure. Basic design criteria and advantages of the ultrasonic−microwave coupled operations in the realized apparatus are presented and discussed. Results of testing and of operating runs to produce shell−core microparticles are also reported, emphasizing the main features of the produced particles.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
This work presents both the design of a novel process to produce microparticles with a shell−core structure and a bench scale apparatus purposely realized. The developed process was designed to respond to mandatory needs of process intensification. It involved the coupling of two emergent technologies: atomization assisted by ultrasonic energy and microwave heating. The former was used to atomize polymeric solutions; the latter was applied to stabilize the produced droplets by drying. Both operations were performed in the same vessel with the aim to have a single-pot process chamber and were carried out by a semicontinuous procedure. Basic design criteria and advantages of the ultrasonic−microwave coupled operations in the realized apparatus are presented and discussed. Results of testing and of operating runs to produce shell−core microparticles are also reported, emphasizing the main features of the produced particles.Bochicchio, Sabrina; Dalmoro, Annalisa; Barba, Anna Angela; Grassi, Gabriele; Lamberti, Gaetano
Liposomes as siRNA Delivery Vectors Journal Article
Current drug metabolism, 15 (9), pp. 882–892, 2014, ISSN: 1389-2002.
@article{Bochicchio2014,
title = {Liposomes as siRNA Delivery Vectors},
author = {Sabrina Bochicchio and Annalisa Dalmoro and Anna Angela Barba and Gabriele Grassi and Gaetano Lamberti},
url = {http://www.eurekaselect.com/128256/article},
doi = {10.2174/1389200216666150206124913},
issn = {1389-2002},
year = {2014},
date = {2014-01-01},
journal = {Current drug metabolism},
volume = {15},
number = {9},
pages = {882--892},
publisher = {Bentham Science Publishers},
abstract = {Nucleic Acid Based Drugs (NABDs) constitute a class of promising and powerful therapeutic new agents with limited side effects, potentially useable against a wide range of diseases, including cancer. Among them, the short interfering RNAs (siRNAs), represent very effective molecules. Despite their in vitro efficacy, the major drawback that limits siRNAs usage consists in a difficult delivery due to their very low stability in physiological fluids, and to their limited membrane-permeability through physiological barriers. On the other hand, the liposomes (lipid bilayers closed in vesicles of various sizes) represent interesting drug delivery systems (DDSs) which can be tailored in order to get the best performance in terms of load, vesicle size and transfection yield. In this work, the current state of study in these two fields, and the connections between them, are briefly summarized.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Nucleic Acid Based Drugs (NABDs) constitute a class of promising and powerful therapeutic new agents with limited side effects, potentially useable against a wide range of diseases, including cancer. Among them, the short interfering RNAs (siRNAs), represent very effective molecules. Despite their in vitro efficacy, the major drawback that limits siRNAs usage consists in a difficult delivery due to their very low stability in physiological fluids, and to their limited membrane-permeability through physiological barriers. On the other hand, the liposomes (lipid bilayers closed in vesicles of various sizes) represent interesting drug delivery systems (DDSs) which can be tailored in order to get the best performance in terms of load, vesicle size and transfection yield. In this work, the current state of study in these two fields, and the connections between them, are briefly summarized.Barba, Anna Angela; Dalmoro, Annalisa; D'Amore, Matteo; Vascello, Clara; Lamberti, Gaetano
Biocompatible nano-micro-particles by solvent evaporation from multiple emulsions technique Journal Article
Journal of Materials Science, 49 (14), pp. 5160–5170, 2014, ISSN: 0022-2461.
@article{Barba2014c,
title = {Biocompatible nano-micro-particles by solvent evaporation from multiple emulsions technique},
author = { Anna Angela Barba and Annalisa Dalmoro and Matteo D'Amore and Clara Vascello and Gaetano Lamberti},
url = {http://link.springer.com/10.1007/s10853-014-8224-1},
doi = {10.1007/s10853-014-8224-1},
issn = {0022-2461},
year = {2014},
date = {2014-01-01},
journal = {Journal of Materials Science},
volume = {49},
number = {14},
pages = {5160--5170},
publisher = {Springer US},
abstract = {In this study, a method based on a multiple emulsions system was developed for the production of polymeric nano and micro-vectors. The possibility to apply an unified preparation technique to different polymers, such as polyesters [polycaprolactone, poly-dl-lactide, poly(dl-lactide-co-caprolactone) = 70/30] and polyacrylates [poly(methylmethacrylate\textendashacrylic acid) = 73/27], loaded with different model molecules (budesonide, tamoxifen, and $alpha$-tocopherol) was explored. After selecting the best operating conditions, especially for emulsification and separation, the technique proved to be readily adaptable for production of both nano and micro-particles with different morphologies, depending on type of polymer, and consequently on solvent used for solubilization: nano-particles, with a round shape and a smooth surface, for polyesters, otherwise micro-particles for the polyacrylate polymer, owing to the presence of hydrophilic co-solvents, that caused both an easy coalescence between the oil and water phases, thus enlarged particles size, and a high porosity. Even the yield of encapsulation was influenced by the presence of hydrophilic co-solvents, causing a higher yield for nano-vectors. Polyesters-based nano-vectors showed release times of molecules, linked to their degradation time, higher than 8 months that make them useful to formulate injectable or implantable drug delivery systems. Polyacrylate-based micro-vectors showed an enteric behavior, interesting for designing solid pharmaceutical formulations for oral delivery. Therefore, the technique demonstrated to assure a broad application in drug delivery research.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In this study, a method based on a multiple emulsions system was developed for the production of polymeric nano and micro-vectors. The possibility to apply an unified preparation technique to different polymers, such as polyesters [polycaprolactone, poly-dl-lactide, poly(dl-lactide-co-caprolactone) = 70/30] and polyacrylates [poly(methylmethacrylate–acrylic acid) = 73/27], loaded with different model molecules (budesonide, tamoxifen, and $alpha$-tocopherol) was explored. After selecting the best operating conditions, especially for emulsification and separation, the technique proved to be readily adaptable for production of both nano and micro-particles with different morphologies, depending on type of polymer, and consequently on solvent used for solubilization: nano-particles, with a round shape and a smooth surface, for polyesters, otherwise micro-particles for the polyacrylate polymer, owing to the presence of hydrophilic co-solvents, that caused both an easy coalescence between the oil and water phases, thus enlarged particles size, and a high porosity. Even the yield of encapsulation was influenced by the presence of hydrophilic co-solvents, causing a higher yield for nano-vectors. Polyesters-based nano-vectors showed release times of molecules, linked to their degradation time, higher than 8 months that make them useful to formulate injectable or implantable drug delivery systems. Polyacrylate-based micro-vectors showed an enteric behavior, interesting for designing solid pharmaceutical formulations for oral delivery. Therefore, the technique demonstrated to assure a broad application in drug delivery research.Barba, Anna Angela; Bochicchio, Sabrina; Lamberti, Gaetano; Dalmoro, Annalisa
Ultrasonic energy in liposome production: process modelling and size calculation Journal Article
Soft Matter, 10 (15), pp. 2574, 2014, ISSN: 1744-683X.
@article{Barba2014a,
title = {Ultrasonic energy in liposome production: process modelling and size calculation},
author = { Anna Angela Barba and Sabrina Bochicchio and Gaetano Lamberti and Annalisa Dalmoro},
url = {http://xlink.rsc.org/?DOI=c3sm52879k},
doi = {10.1039/c3sm52879k},
issn = {1744-683X},
year = {2014},
date = {2014-01-01},
journal = {Soft Matter},
volume = {10},
number = {15},
pages = {2574},
publisher = {The Royal Society of Chemistry},
abstract = {The use of liposomes in several fields of biotechnology, as well as in pharmaceutical and food sciences is continuously increasing. Liposomes can be used as carriers for drugs and other active molecules. Among other characteristics, one of the main features relevant to their target applications is the liposome size. The size of liposomes, which is determined during the production process, decreases due to the addition of energy. The energy is used to break the lipid bilayer into smaller pieces, then these pieces close themselves in spherical structures. In this work, the mechanisms of rupture of the lipid bilayer and the formation of spheres were modelled, accounting for how the energy, supplied by ultrasonic radiation, is stored within the layers, as the elastic energy due to the curvature and as the tension energy due to the edge, and to account for the kinetics of the bending phenomenon. An algorithm to solve the model equations was designed and the relative calculation code was written. A dedicated preparation protocol, which involves active periods during which the energy is supplied and passive periods during which the energy supply is set to zero, was defined and applied. The model predictions compare well with the experimental results, by using the energy supply rate and the time constant as fitting parameters. Working with liposomes of different sizes as the starting point of the experiments, the key parameter is the ratio between the energy supply rate and the initial surface area.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The use of liposomes in several fields of biotechnology, as well as in pharmaceutical and food sciences is continuously increasing. Liposomes can be used as carriers for drugs and other active molecules. Among other characteristics, one of the main features relevant to their target applications is the liposome size. The size of liposomes, which is determined during the production process, decreases due to the addition of energy. The energy is used to break the lipid bilayer into smaller pieces, then these pieces close themselves in spherical structures. In this work, the mechanisms of rupture of the lipid bilayer and the formation of spheres were modelled, accounting for how the energy, supplied by ultrasonic radiation, is stored within the layers, as the elastic energy due to the curvature and as the tension energy due to the edge, and to account for the kinetics of the bending phenomenon. An algorithm to solve the model equations was designed and the relative calculation code was written. A dedicated preparation protocol, which involves active periods during which the energy is supplied and passive periods during which the energy supply is set to zero, was defined and applied. The model predictions compare well with the experimental results, by using the energy supply rate and the time constant as fitting parameters. Working with liposomes of different sizes as the starting point of the experiments, the key parameter is the ratio between the energy supply rate and the initial surface area.2013
Barba, Anna Angela; Dalmoro, Annalisa; D'Amore, Matteo; Lamberti, Gaetano
In vitro dissolution of pH sensitive microparticles for colon-specific drug delivery Journal Article
Pharmaceutical Development and Technology, 18 (6), pp. 1399–1406, 2013, ISSN: 1083-7450.
@article{Barba2013b,
title = {In vitro dissolution of pH sensitive microparticles for colon-specific drug delivery},
author = { Anna Angela Barba and Annalisa Dalmoro and Matteo D'Amore and Gaetano Lamberti},
url = {http://www.tandfonline.com/doi/full/10.3109/10837450.2012.727005},
doi = {10.3109/10837450.2012.727005},
issn = {1083-7450},
year = {2013},
date = {2013-12-01},
journal = {Pharmaceutical Development and Technology},
volume = {18},
number = {6},
pages = {1399--1406},
publisher = {Taylor & Francis},
abstract = {Objective: The objective of this work is to prepare oral dosage systems based on enteric materials in order to verify their possible use as Colon-Specific Drug Delivery Systems (CSDDSs). Methodology: In particular, three different copolymers of methyl-methacrylate (MMA) - acrylic acid (AA) are synthesized with increasing percentage of MMA (from 70% to 73%) and they are used to produce microparticles by the double-emulsion solvent evaporation method. The microparticles, loaded using theophylline as model drug, are then tested for drug release under varying pH to reproduce what happens in the human GI tract.Results: All the investigated systems have shown an effective pH sensitiveness: they show a good gastro-resistance, releasing the model drug only at higher pH, small intestine or colon, depending on the kind of used copolymer. Conclusion: The results confirm the usefulness of both the materials and the methods proposed in this study for colon-specific delivery applications.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Objective: The objective of this work is to prepare oral dosage systems based on enteric materials in order to verify their possible use as Colon-Specific Drug Delivery Systems (CSDDSs). Methodology: In particular, three different copolymers of methyl-methacrylate (MMA) - acrylic acid (AA) are synthesized with increasing percentage of MMA (from 70% to 73%) and they are used to produce microparticles by the double-emulsion solvent evaporation method. The microparticles, loaded using theophylline as model drug, are then tested for drug release under varying pH to reproduce what happens in the human GI tract.Results: All the investigated systems have shown an effective pH sensitiveness: they show a good gastro-resistance, releasing the model drug only at higher pH, small intestine or colon, depending on the kind of used copolymer. Conclusion: The results confirm the usefulness of both the materials and the methods proposed in this study for colon-specific delivery applications.Dalmoro, Annalisa; Barba, Anna Angela; D'Amore, Matteo
Analysis of Size Correlations for Microdroplets Produced by Ultrasonic Atomization Journal Article
The Scientific World Journal, 2013 , pp. 1–7, 2013, ISSN: 1537-744X.
@article{author,
title = {Analysis of Size Correlations for Microdroplets Produced by Ultrasonic Atomization},
author = { Annalisa Dalmoro and Anna Angela Barba and Matteo D'Amore},
url = {http://www.hindawi.com/journals/tswj/2013/482910/},
doi = {10.1155/2013/482910},
issn = {1537-744X},
year = {2013},
date = {2013-01-01},
journal = {The Scientific World Journal},
volume = {2013},
pages = {1--7},
abstract = {Microencapsulation techniques are widely applied in the field of pharmaceutical production to control drugs release in time and in physiological environments. Ultrasonic-assisted atomization is a new technique to produce microencapsulated systems by a mechanical approach. Interest in this technique is due to the advantages evidenceable (low level of mechanical stress in materials, reduced energy request, reduced apparatuses size) when comparing it to more conventional techniques. In this paper, the groundwork of atomization is introduced, the role of relevant parameters in ultrasonic atomization mechanism is discussed, and correlations to predict droplets size starting from process parameters and material properties are presented and tested.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Microencapsulation techniques are widely applied in the field of pharmaceutical production to control drugs release in time and in physiological environments. Ultrasonic-assisted atomization is a new technique to produce microencapsulated systems by a mechanical approach. Interest in this technique is due to the advantages evidenceable (low level of mechanical stress in materials, reduced energy request, reduced apparatuses size) when comparing it to more conventional techniques. In this paper, the groundwork of atomization is introduced, the role of relevant parameters in ultrasonic atomization mechanism is discussed, and correlations to predict droplets size starting from process parameters and material properties are presented and tested.Grassi, Gabriele; Scaggiante, B; Dapas, B; Farra, R; Tonon, F; Lamberti, Gaetano; Barba, Anna Angela; Fiorentino, S; Fiotti, N; Zanconati, F; Abrami, Michela; Grassi, Mario
Therapeutic Potential of Nucleic Acid-Based Drugs in Coronary Hyper- Proliferative Vascular Diseases Journal Article
Current Medicinal Chemistry, 20 (28), pp. 3515–3538, 2013, ISSN: 09298673.
@article{Grassi2013,
title = {Therapeutic Potential of Nucleic Acid-Based Drugs in Coronary Hyper- Proliferative Vascular Diseases},
author = { Gabriele Grassi and B Scaggiante and B Dapas and R Farra and F Tonon and Gaetano Lamberti and Anna Angela Barba and S Fiorentino and N Fiotti and F Zanconati and Michela Abrami and Mario Grassi},
url = {http://www.eurekaselect.com/openurl/content.php?genre=article&issn=0929-8673&volume=20&issue=28&spage=3515},
doi = {10.2174/09298673113209990031},
issn = {09298673},
year = {2013},
date = {2013-01-01},
journal = {Current Medicinal Chemistry},
volume = {20},
number = {28},
pages = {3515--3538},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Dalmoro, Annalisa; D'Amore, Matteo; Barba, Anna Angela
Droplet size prediction in the production of drug delivery microsystems by ultrasonic atomization. Journal Article
Translational medicine @ UniSa, 7 (2), pp. 6–11, 2013, ISSN: 2239-9747.
@article{Dalmoro2013,
title = {Droplet size prediction in the production of drug delivery microsystems by ultrasonic atomization.},
author = { Annalisa Dalmoro and Matteo D'Amore and Anna Angela Barba},
url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3829785&tool=pmcentrez&rendertype=abstract},
issn = {2239-9747},
year = {2013},
date = {2013-01-01},
journal = {Translational medicine @ UniSa},
volume = {7},
number = {2},
pages = {6--11},
publisher = {Universit},
abstract = {Microencapsulation processes of drugs or other functional molecules are of great interest in pharmaceutical production fields. Ultrasonic assisted atomization is a new technique to produce microencapsulated systems by mechanical approach. It seems to offer several advantages (low level of mechanical stress in materials, reduced energy request, reduced apparatuses size) with respect to more conventional techniques. In this paper the groundwork of atomization is briefly introduced and correlations to predict droplet size starting from process parameters and material properties are presented.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Microencapsulation processes of drugs or other functional molecules are of great interest in pharmaceutical production fields. Ultrasonic assisted atomization is a new technique to produce microencapsulated systems by mechanical approach. It seems to offer several advantages (low level of mechanical stress in materials, reduced energy request, reduced apparatuses size) with respect to more conventional techniques. In this paper the groundwork of atomization is briefly introduced and correlations to predict droplet size starting from process parameters and material properties are presented.2012
Cascone, Sara; Lamberti, Gaetano; Titomanlio, Giuseppe; Barba, Anna Angela; D'Amore, Matteo
Microencapsulation effectiveness of small active molecules in biopolymer by ultrasonic atomization technique Journal Article
Drug Development and Industrial Pharmacy, 38 (12), pp. 1486–1493, 2012, ISSN: 0363-9045.
@article{Cascone2012,
title = {Microencapsulation effectiveness of small active molecules in biopolymer by ultrasonic atomization technique},
author = { Sara Cascone and Gaetano Lamberti and Giuseppe Titomanlio and Anna Angela Barba and Matteo D'Amore},
url = {http://www.tandfonline.com/doi/full/10.3109/03639045.2011.653814},
doi = {10.3109/03639045.2011.653814},
issn = {0363-9045},
year = {2012},
date = {2012-12-01},
journal = {Drug Development and Industrial Pharmacy},
volume = {38},
number = {12},
pages = {1486--1493},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Dalmoro, Annalisa; Barba, Anna Angela; Lamberti, Gaetano; Grassi, Mario; D'Amore, Matteo
Pharmaceutical applications of biocompatible polymer blends containing sodium alginate Journal Article
Advances in Polymer Technology, 31 (3), pp. 219–230, 2012, ISSN: 07306679.
@article{Dalmoro2012a,
title = {Pharmaceutical applications of biocompatible polymer blends containing sodium alginate},
author = { Annalisa Dalmoro and Anna Angela Barba and Gaetano Lamberti and Mario Grassi and Matteo D'Amore},
url = {http://doi.wiley.com/10.1002/adv.21276},
doi = {10.1002/adv.21276},
issn = {07306679},
year = {2012},
date = {2012-09-01},
journal = {Advances in Polymer Technology},
volume = {31},
number = {3},
pages = {219--230},
publisher = {Wiley Subscription Services, Inc., A Wiley Company},
abstract = {Biocompatible polymer blends, such as alginate blends, have a widespread use in pharmaceutical and medical applications due to their specific features, such as biodegradation, adhesiveness, and thermo- and pH sensitivity and that can be obtained from the mixture composition. In this work, the use of alginate blends was tested in a novel production methodology of therapeutic dosage forms based on polymeric chain reticulation phenomena induced by exposure to bivalent ions. Two kinds of sodium alginate were used to obtain gel films (structured films) in blends with Pluronic F127®. The blends were considered for applications in gel paving of drug-eluting stents. Sodium alginate was also used in shell\textendashcore particle production (structured particles) to obtain shell-barrier reducing drug release in the preparative steps (see wash operations). Both structures, films and particles, were obtained using Cu2+ and Ca2+ ions, respectively. Film/shell barrier properties were tested in dissolution experiments using vitamin B12 as an active molecule model. Experimental work demonstrated that the alginate composition is a crucial point in defining reticulated structures.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Biocompatible polymer blends, such as alginate blends, have a widespread use in pharmaceutical and medical applications due to their specific features, such as biodegradation, adhesiveness, and thermo- and pH sensitivity and that can be obtained from the mixture composition. In this work, the use of alginate blends was tested in a novel production methodology of therapeutic dosage forms based on polymeric chain reticulation phenomena induced by exposure to bivalent ions. Two kinds of sodium alginate were used to obtain gel films (structured films) in blends with Pluronic F127®. The blends were considered for applications in gel paving of drug-eluting stents. Sodium alginate was also used in shell–core particle production (structured particles) to obtain shell-barrier reducing drug release in the preparative steps (see wash operations). Both structures, films and particles, were obtained using Cu2+ and Ca2+ ions, respectively. Film/shell barrier properties were tested in dissolution experiments using vitamin B12 as an active molecule model. Experimental work demonstrated that the alginate composition is a crucial point in defining reticulated structures.Dalmoro, Annalisa; Barba, Anna Angela; Lamberti, Gaetano; D'Amore, Matteo
Intensifying the microencapsulation process: Ultrasonic atomization as an innovative approach Journal Article
European Journal of Pharmaceutics and Biopharmaceutics, 80 (3), pp. 471–477, 2012, ISSN: 09396411.
@article{Dalmoro2012,
title = {Intensifying the microencapsulation process: Ultrasonic atomization as an innovative approach},
author = { Annalisa Dalmoro and Anna Angela Barba and Gaetano Lamberti and Matteo D'Amore},
url = {http://www.sciencedirect.com/science/article/pii/S0939641112000070},
doi = {10.1016/j.ejpb.2012.01.006},
issn = {09396411},
year = {2012},
date = {2012-04-01},
journal = {European Journal of Pharmaceutics and Biopharmaceutics},
volume = {80},
number = {3},
pages = {471--477},
abstract = {In this review, new approaches to the microencapsulation processes, widely used in the manufacturing of pharmaceutical products, are discussed focusing the attention on the emerging ultrasonic atomization technique. Fundamentals and novel aspects are presented, and advantages of ultrasonic atomization in terms of intensification and low energy requests are emphasized.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In this review, new approaches to the microencapsulation processes, widely used in the manufacturing of pharmaceutical products, are discussed focusing the attention on the emerging ultrasonic atomization technique. Fundamentals and novel aspects are presented, and advantages of ultrasonic atomization in terms of intensification and low energy requests are emphasized.Barba, Anna Angela; Dalmoro, Annalisa; D'Amore, Matteo; Lamberti, Gaetano
Controlled Release of Drugs from Microparticles Produced by Ultrasonic Assisted Atomization Based on Biocompatible Polymers Journal Article
Chemical and Biochemical Engineering Quarterly, 26 (4), pp. 345–353, 2012, ISSN: 0352-9568.
@article{Barba2012b,
title = {Controlled Release of Drugs from Microparticles Produced by Ultrasonic Assisted Atomization Based on Biocompatible Polymers},
author = { Anna Angela Barba and Annalisa Dalmoro and Matteo D'Amore and Gaetano Lamberti},
url = {http://hrcak.srce.hr/index.php?show=clanak&id_clanak_jezik=138369},
issn = {0352-9568},
year = {2012},
date = {2012-01-01},
journal = {Chemical and Biochemical Engineering Quarterly},
volume = {26},
number = {4},
pages = {345--353},
publisher = {Hrvatsko dru\v{s}tvo kemijskih in\v{z}enjera i tehnologa},
abstract = {Microencapsulation of active molecules in biocompatible polymers is a matter of great interest in pharmaceutical sciences. Ultrasonic assisted atomization as a new technique to produce microencapsulated systems seems to offer several advantages (low level of mechanical stress in materials, reduced energy request, reduced apparatuses size) with respect to more conventional techniques. In this work, fine drug-loaded particles were produced by ionic reticulation of droplets obtained by ultrasonic atomization of biopolymers solutions. The particles were then characterized in terms of morphology and drug release kinetics. Data were used to estimate the PNMS (Polymeric Network Mesh-Size) with the aims of clarifying its role in controlled drug release, and analyzing its relationships with material and process parameters. For materials and operative conditions investigated, the calculated PNMS was found consistent with a fast release of drugs of small molecular size.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Microencapsulation of active molecules in biocompatible polymers is a matter of great interest in pharmaceutical sciences. Ultrasonic assisted atomization as a new technique to produce microencapsulated systems seems to offer several advantages (low level of mechanical stress in materials, reduced energy request, reduced apparatuses size) with respect to more conventional techniques. In this work, fine drug-loaded particles were produced by ionic reticulation of droplets obtained by ultrasonic atomization of biopolymers solutions. The particles were then characterized in terms of morphology and drug release kinetics. Data were used to estimate the PNMS (Polymeric Network Mesh-Size) with the aims of clarifying its role in controlled drug release, and analyzing its relationships with material and process parameters. For materials and operative conditions investigated, the calculated PNMS was found consistent with a fast release of drugs of small molecular size.Barba, Anna Angela; Dalmoro, Annalisa; D'Amore, Matteo
An engineering approach to biomedical sciences: advanced strategies in drug delivery systems production Journal Article
Translational Medicine@ UniSa, 4 , pp. 5–11, 2012.
@article{Barba2012a,
title = {An engineering approach to biomedical sciences: advanced strategies in drug delivery systems production},
author = { Anna Angela Barba and Annalisa Dalmoro and Matteo D'Amore},
year = {2012},
date = {2012-01-01},
journal = {Translational Medicine@ UniSa},
volume = {4},
pages = {5--11},
publisher = {Universit},
abstract = {Development and optimization of novel production techniques for drug delivery systems are fundamental steps in the “from the bench to the bedside” process which is the base of translational medicine. In particular, in the current scenery where the need for reducing energy consumption, emissions, wastes and risks drives the development of sustainable processes, new pharmaceutical manufacturing does not constitute an exception. In this paper, concepts of process intensification are presented and their transposition in drug delivery systems production is discussed. Moreover, some examples on intensified techniques, for drug microencapsulation and granules drying, are reported.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Development and optimization of novel production techniques for drug delivery systems are fundamental steps in the “from the bench to the bedside” process which is the base of translational medicine. In particular, in the current scenery where the need for reducing energy consumption, emissions, wastes and risks drives the development of sustainable processes, new pharmaceutical manufacturing does not constitute an exception. In this paper, concepts of process intensification are presented and their transposition in drug delivery systems production is discussed. Moreover, some examples on intensified techniques, for drug microencapsulation and granules drying, are reported.2010
Dalmoro, Annalisa; Lamberti, Gaetano; Titomanlio, Giuseppe; Barba, Anna Angela; D'Amore, Matteo
Enteric Micro-Particles for Targeted Oral Drug Delivery Journal Article
AAPS PharmSciTech, 11 (4), pp. 1500–1507, 2010, ISSN: 1530-9932.
@article{Dalmoro2010a,
title = {Enteric Micro-Particles for Targeted Oral Drug Delivery},
author = { Annalisa Dalmoro and Gaetano Lamberti and Giuseppe Titomanlio and Anna Angela Barba and Matteo D'Amore},
url = {http://www.springerlink.com/index/10.1208/s12249-010-9528-3},
doi = {10.1208/s12249-010-9528-3},
issn = {1530-9932},
year = {2010},
date = {2010-12-01},
journal = {AAPS PharmSciTech},
volume = {11},
number = {4},
pages = {1500--1507},
publisher = {Springer US},
abstract = {This work is focused on production of enteric-coated micro-particles for oral administration, using a water-in-oil-in-water solvent evaporation technique. The active agent theophylline was first encapsulated in cellulose acetate phthalate (CAP), a pH-sensitive well-known polymer, which is insoluble in acid media but dissolves at neutral pH (above pH 6). In this first step, CAP was chosen with the aim optimizing the preparation and characterization methods. The desired release pattern has been obtained (low release at low pH, higher release at neutral pH) but in presence of a low encapsulation efficiency. Then, the CAP was replaced by a novel-synthesized pH-sensitive poly(methyl methacrylate\textendashacrylic acid) copolymer, poly(MMA\textendashAA). In this second step, the role of two process parameters was investigated, i.e., the percentage of emulsion stabilizer (polyvinyl alcohol, PVA) and the stirring power for the double emulsion on the encapsulation efficiency. The encapsulation efficiency was found to increase with PVA percentage and to decrease with the stirring power. By increasing the PVA content and by decreasing the stirring power, a high stable double emulsion was obtained, and this explains the increase in encapsulation efficiency found.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
This work is focused on production of enteric-coated micro-particles for oral administration, using a water-in-oil-in-water solvent evaporation technique. The active agent theophylline was first encapsulated in cellulose acetate phthalate (CAP), a pH-sensitive well-known polymer, which is insoluble in acid media but dissolves at neutral pH (above pH 6). In this first step, CAP was chosen with the aim optimizing the preparation and characterization methods. The desired release pattern has been obtained (low release at low pH, higher release at neutral pH) but in presence of a low encapsulation efficiency. Then, the CAP was replaced by a novel-synthesized pH-sensitive poly(methyl methacrylate–acrylic acid) copolymer, poly(MMA–AA). In this second step, the role of two process parameters was investigated, i.e., the percentage of emulsion stabilizer (polyvinyl alcohol, PVA) and the stirring power for the double emulsion on the encapsulation efficiency. The encapsulation efficiency was found to increase with PVA percentage and to decrease with the stirring power. By increasing the PVA content and by decreasing the stirring power, a high stable double emulsion was obtained, and this explains the increase in encapsulation efficiency found.Dalmoro, Annalisa; Villano, Oriana; Barba, Anna Angela; Lamberti, Gaetano
Dosare dove serve Journal Article
NCF-Notiziario Chimico Farmaceutico, 49 (4), pp. 112–114, 2010, ISSN: 0393-3733.
@article{Dalmoro2010,
title = {Dosare dove serve},
author = { Annalisa Dalmoro and Oriana Villano and Anna Angela Barba and Gaetano Lamberti},
issn = {0393-3733},
year = {2010},
date = {2010-01-01},
journal = {NCF-Notiziario Chimico Farmaceutico},
volume = {49},
number = {4},
pages = {112--114},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2009
Barba, Anna Angela; D'Amore, Matteo; Cascone, Sara; Lamberti, Gaetano; Titomanlio, Giuseppe
Intensification of biopolymeric microparticles production by ultrasonic assisted atomization Journal Article
Chemical Engineering and Processing: Process Intensification, 48 (10), pp. 1477–1483, 2009, ISSN: 02552701.
@article{Barba2009g,
title = {Intensification of biopolymeric microparticles production by ultrasonic assisted atomization},
author = { Anna Angela Barba and Matteo D'Amore and Sara Cascone and Gaetano Lamberti and Giuseppe Titomanlio},
url = {http://www.sciencedirect.com/science/article/pii/S0255270109001524},
doi = {10.1016/j.cep.2009.08.004},
issn = {02552701},
year = {2009},
date = {2009-01-01},
journal = {Chemical Engineering and Processing: Process Intensification},
volume = {48},
number = {10},
pages = {1477--1483},
abstract = {In this work ultrasonic atomization process is applied to produce biopolymer microparticles with potential applications in pharmaceutical and nutraceutical fields. Natural polymer (alginate)/water solution is atomized by ultrasonic assisted process and the droplets spray is reticulated using a solution of copper sulfate, where the Cu2+ ions cause the formation of a network structure (hard porous gel). Several operating parameters (solution concentration, flow rate, atomization power) are changed to study their effects on the produced microparticles. Literature correlations able to predict the features of the droplets as functions of process parameters are optimized using a statistical approach. Furthermore, the energy requirement for the drops production is compared with the energy required by traditional techniques to evaluate the intensification effect of the ultrasonic on the atomization process.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
In this work ultrasonic atomization process is applied to produce biopolymer microparticles with potential applications in pharmaceutical and nutraceutical fields. Natural polymer (alginate)/water solution is atomized by ultrasonic assisted process and the droplets spray is reticulated using a solution of copper sulfate, where the Cu2+ ions cause the formation of a network structure (hard porous gel). Several operating parameters (solution concentration, flow rate, atomization power) are changed to study their effects on the produced microparticles. Literature correlations able to predict the features of the droplets as functions of process parameters are optimized using a statistical approach. Furthermore, the energy requirement for the drops production is compared with the energy required by traditional techniques to evaluate the intensification effect of the ultrasonic on the atomization process.