Annalisa Dalmoro
Assegnista di ricerca
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Curriculum Accademico
Annalisa Dalmoro si è laureata in Ingegneria Chimica, con lode, nel marzo 2009, ha conseguito il titolo di dottore di ricerca in Dottorato di ricerca in Scienze e tecnologie per l’industria chimica, farmaceutica e alimentare – Ingegneria Chimica nel 2013. Da aprile 2013 ha usufruito di un contratto di collaborazione con il Dipartimento di Ingegneria Industriale e di due assegni di ricerca annuali presso il Dipartimento di Farmacia dell’Università degli Studi di Salerno, uno dei quali ancora in corso.
L’attività di ricerca dell’Ing. Annalisa Dalmoro è stata svolta presso i laboratori del gruppo TPP (www.minerva.unisa.it) dell’Università di Salerno, anche con contratti di collaborazione, sui processi di produzione di forme farmaceutiche solide utilizzando metodiche diverse e sullo sviluppo di materiali per applicazioni biomediche. In particolare, ha focalizzato il suo lavoro sulla progettazione e costruzione di un impianto semicontinuo di produzione di micro particelle di tipo shell-core utilizzando due tecnologie non convenzionali, quali atomizzazione ad ultrasuoni ed essiccamento a microonde; sulla produzione di micro e nano sistemi tramite emulsioni multiple, ottenute tramite energia ultrasonica; sulla sintesi di polimeri enterici per applicazioni farmaceutiche; sullo studio della reticolazione degli alginati in miscele alginato/pluronico con annesso studio sull’applicabilità di tali miscele per la ricopertura in-situ di stent coronarici. Inoltre, si è occupata anche di processi di granulazione per la stabilizzazione di mangimi ad uso zootecnico, di stabilizzazione di agenti schiumanti per uso alimentare tramite spray drying e di trattamento di frutta, cereali e legumi tramite microonde, attraverso progetti di collaborazione con aziende.
La sua attività didattica è consistita in seminari monografici e collaborazioni nell’ambito dei corsi di Rilascio e direzionamento dei farmaci (A.A. 2011/2012-2012/2013-2013/2014), Impianti dell’Industria farmaceutica (A.A. 2011/2012), Impianti e processi dell’industria farmaceutica (A.A. 2012/2013 – 2013/2014 ), Analisi dei prodotti cosmetici (A.A. 2013/2014). Ha partecipato come cultore della materia alle commissioni d’esame: dall’anno accademico 2010/2011 all’anno accademico 2012/2013 dei corsi di Principi di Ingegneria Chimica e di Impianti dell’Industria Farmaceutica, nell’anno accademico 2011/2012 del corso di Reattori Chimici, nell’anno accademico 2012/2013 del corso di Fenomeni di Trasporto in processi alimentari, dall’anno accademico 2010/2011 all’anno accademico 2013/2014 del corso di Impianti chimici dell’industria farmaceutica, nell’anno accademico 2013/2014 dei corsi di Rilascio e direzionamento dei farmaci e di Analisi dei prodotti cosmetici. Ha inoltre effettuato tutoraggio per lo svolgimento di 17 tesi di laurea, di cui 12 in Ingegneria Chimica, 3 in Farmacia e 2 in Chimica e Tecnologia Farmaceutiche.
È stata revisore per le seguenti riviste internazionali: Journal of Microencapsulation, Journal of Chemical Technology & Biotechnology, Industrial & Engineering Chemistry Research.
Ha prodotto 39 lavori di cui 20 sono pubblicazioni su rivista internazionale (di cui tre in corso di revisione); 14 sono comunicazioni a convegni internazionali; 4 sono comunicazioni a convegni nazionali e 1 è un articolo pubblicato su giornali nazionali.
Tesi
Tesi di dottorato di ricerca
- Annalisa Dalmoro, Novel technologies and process intensification in the production of micro-systems with pharmacological/nutraceutical activity (estratto della tesi PDF, tesi completa PDF 2 MB), Tesi di Dottorato di Ricerca in Scienza e Tecnologie per l’Industria Chimica, Farmaceutica e Alimentare”, Ingegneria Chimica (XI Ciclo-Nuova Serie), Relatori: Prof. Ing. Matteo d’Amore, Prof. Ing. Anna Angela Barba, Comitato scientifico: Prof. Roland Bodmeier (Freie Universität Berlin), Prof. Nadia Passerini (Università di Bologna)
Tesi di secondo livello
- Annalisa Dalmoro, Enteric microparticles coated with smart polymers for controlled drug delivery applications (estratto della tesi PDF, tesi completa PDF 5.5 MB), Laurea Specialistica in Ingegneria Chimica, 27/03/2009, Relatori: Prof. Ing. Giuseppe Titomanlio, Prof. Ing. Gaetano Lamberti
Tesi di laurea di primo livello
- Annalisa Dalmoro, Analisi dei fenomeni di trasporto dell’acqua in compresse di idrogeli rigonfianti (estratto della tesi PDF, tesi completa PDF 2.4 MB), Laurea in Ingegneria Chimica, 31/10/2006, Relatori: Prof. Ing. Giuseppe Titomanlio, Prof. Ing. Gaetano Lamberti (Questa tesi è risultata vincitrice del premio nazionale AIDIC-GRICU come la migliore tesi di laurea di primo livello in ingegneria chimica in Italia nel 2006)
Pubblicazioni
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. Abstract | Links | BibTeX | Tags: clinical trials, liposomes, Micro and Nano Vectors, NABDs, siRNA @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 = {clinical trials, liposomes, Micro and Nano Vectors, NABDs, siRNA}, 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 drugs |
Dalmoro, 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. Abstract | Links | BibTeX | Tags: Drug Delivery Systems, Micro and Nano Vectors @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 = {Drug Delivery Systems, Micro and Nano Vectors}, 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. Abstract | Links | BibTeX | Tags: Micro and Nano Vectors @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 = {Micro and Nano Vectors}, 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. Abstract | Links | BibTeX | Tags: Micro and Nano Vectors @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 = {Micro and Nano Vectors}, 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. Abstract | Links | BibTeX | Tags: Micro and Nano Vectors, microencapsulation, ultrasonic atomization @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 = {Micro and Nano Vectors, microencapsulation, ultrasonic atomization}, 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). |
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. Abstract | Links | BibTeX | Tags: Micro and Nano Vectors @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 = {Micro and Nano Vectors}, 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. |
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. Abstract | Links | BibTeX | Tags: Micro and Nano Vectors @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 = {Micro and Nano Vectors}, 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 |
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. Abstract | Links | BibTeX | Tags: Micro and Nano Vectors @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 = {Micro and Nano Vectors}, 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. Abstract | Links | BibTeX | Tags: Biopolymer, Micro and Nano Vectors, multiple emulsions, nanoparticles, solvent evaporation @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 = {Biopolymer, Micro and Nano Vectors, multiple emulsions, nanoparticles, solvent evaporation}, 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; 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. Abstract | Links | BibTeX | Tags: drug delivery, Micro and Nano Vectors, Microwave drying, Shell{–}core microparticles, Ultrasonic energy, Vitamins @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 = {drug delivery, Micro and Nano Vectors, Microwave drying, Shell{\textendash}core microparticles, Ultrasonic energy, Vitamins}, 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. Abstract | Links | BibTeX | Tags: Micro and Nano Vectors @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 = {Micro and Nano Vectors}, 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. Abstract | Links | BibTeX | Tags: Drug Delivery Systems, liposome, Micro and Nano Vectors, siRNA @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 = {Drug Delivery Systems, liposome, Micro and Nano Vectors, siRNA}, 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. Abstract | Links | BibTeX | Tags: Micro and Nano Vectors @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 = {Micro and Nano Vectors}, 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. Abstract | Links | BibTeX | Tags: Micro and Nano Vectors @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 = {Micro and Nano Vectors}, 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. Abstract | Links | BibTeX | Tags: Micro and Nano Vectors @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 = {Micro and Nano Vectors}, 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. Abstract | Links | BibTeX | Tags: Micro and Nano Vectors @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 = {Micro and Nano Vectors}, 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. |
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. Abstract | Links | BibTeX | Tags: dimensionless, Micro and Nano Vectors, microparticles size prediction, numbers in atomization, ultrasonic atomization @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 = {dimensionless, Micro and Nano Vectors, microparticles size prediction, numbers in atomization, ultrasonic atomization}, 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 |
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. Abstract | Links | BibTeX | Tags: Alginate gel film, Alginate shell{–}core particles, Biocompatibility, Crosslinking, Hydrogel Characterization, Hydrogels, Micro and Nano Vectors @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 = {Alginate gel film, Alginate shell{\textendash}core particles, Biocompatibility, Crosslinking, Hydrogel Characterization, Hydrogels, Micro and Nano Vectors}, 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. Abstract | Links | BibTeX | Tags: Atomization assisted by ultrasonic energy, Micro and Nano Vectors, microencapsulation, Microparticles production, Process intensification @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 = {Atomization assisted by ultrasonic energy, Micro and Nano Vectors, microencapsulation, Microparticles production, Process intensification}, 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. Abstract | Links | BibTeX | Tags: Micro and Nano Vectors @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 = {Micro and Nano Vectors}, 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. Abstract | BibTeX | Tags: Micro and Nano Vectors, microwave heating, Process intensification, ultrasonic atomization @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 = {Micro and Nano Vectors, microwave heating, Process intensification, ultrasonic atomization}, 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. Abstract | Links | BibTeX | Tags: coating, drug targeting, emulsion, Micro and Nano Vectors, microencapsulation, polymeric drug delivery systems @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 = {coating, drug targeting, emulsion, Micro and Nano Vectors, microencapsulation, polymeric drug delivery systems}, 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. BibTeX | Tags: Micro and Nano Vectors @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 = {Micro and Nano Vectors}, pubstate = {published}, tppubtype = {article} } |