@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 = {Micro and Nano Vectors},

pubstate = {published},

tppubtype = {article}

}

@article{Kazlauske2017,

title = {Determination of the release mechanism of Theophylline from pellets coated with Surelease® − a water dispersion of Ethyl cellulose},

author = {Jurgita Kazlauske and Maria Margherita Cafaro and Diego Caccavo and Maria Grazia Marucci and Gaetano Lamberti and Anna Angela Barba and Anette Larsson},

url = {http://www.sciencedirect.com/science/article/pii/S0378517317304970},

doi = {10.1016/j.ijpharm.2017.05.073},

issn = {0378-5173},

year  = {2017},

date = {2017-06-17},

journal = {International Journal of Pharmaceutics},

volume = {528},

number = {1-2},

pages = {345-353},

abstract = {The aim of this study was to investigate the water transport over free standing films based on the aqueous ethyl cellulose (EC) coating Surelease® and the drug (Theophylline) release mechanism from coated pellets. It was found that the main drug release rate from pellets was controlled by a diffusion mechanism. However, the drug release rate was altered by addition of sodium chloride to the external release medium. A decrease in the drug release rate when sodium chloride is added to the release medium has traditionally been used to indicate an osmotic drug release mechanism. However, our findings that the release rate decreased by sodium chloride addition could be explained by sodium chloride diffusing through the coating layer into the inner parts of the pellets, decreasing the solubility of Theophylline. This gave a reduced drug concentration gradient over the coating layer and thus a slower release rate. Furthermore, this study shows, as expected, that the transport of water through Surelease® films into the pellets was faster than the transport out of Theophylline (approx. seven times), which was the reason why the pellets were swelling during the release. It was also shown that the drug release rate, determined for both whole dose release and for single pellets, decreased with increasing thickness (from 16 to 51 μm) of the coating layer controlling the drug release rate.},

keywords = {Drug Delivery Systems, drug release, Hydrogel Characterization},

pubstate = {published},

tppubtype = {article}

}

@article{Caccavo2017b,

title = {Mathematical modeling of the drug release from an ensemble of coated pellets},

author = {Diego Caccavo and Gaetano Lamberti and Maria Margherita Cafaro and Anna Angela Barba and Jurgita Kazlauske and Anette Larsson},

url = {http://onlinelibrary.wiley.com/doi/10.1111/bph.13776/abstract},

doi = {10.1111/bph.13776},

isbn = {1476-5381},

year  = {2017},

date = {2017-04-22},

journal = {British Journal of Pharmacology},

volume = {174},

number = {12},

pages = {1797\textendash1809 },

abstract = {Background and Purpose

Coated pellets are widely used as oral drug delivery systems, being highly accepted by patients and with several advantages with respect to single unit devices. The understanding of their behavior is therefore needed to improve the formulation effectiveness and to reduce the production costs. In spite of such an importance, not many mathematical modeling attempts have been made, mostly due to the complexities arising from the system polydispersity (non homogeneous multiple-unit particulate systems), which has been scarcely investigated with the aid of mechanistic models.



Experimental approach

In this work a mechanistic mathematical model able to describe the single pellet behavior in terms of hydration, drug dissolution, diffusion and release, and particle size change was developed. This model was then extended to describe and predict the behavior of mono- and poly-disperse ensembles of pellets.



Key Results

In particular the polydispersity arising from the inert core size distribution was proved to have a minimal effect on the drug release profile, whereas the size distribution of the polymeric film thickness showed to be the key parameter determining the drug release.



Conclusions and Implications

The developed mechanistic model, capable of considering the polydispersity of the system, was able to predict the release kinetics from ensembles of pellets and to highlight the key parameters to control in the production of pellets-based drug delivery systems, demonstrating its use as a powerful predictive tool.},

keywords = {Drug Delivery Systems, drug release, Hydrogel Characterization, Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@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 = {Micro and Nano Vectors},

pubstate = {published},

tppubtype = {article}

}

@article{Piazza2016,

title = {Cyclin D1 gene silencing by siRNA in ex vivo human tissues cultures},

author = {Ornella Piazza and Ilaria Russo and Sabrina Bochicchio and Anna Angela Barba and Gaetano Lamberti and Pio Zeppa and Vincenzo {Di Crescenzo} and Albino Carrizzo and Carmine Vecchione and Carolina Ciacci},

url = {https://www.gruppotpp.it/wp-content/uploads/2017/03/10.-Piazza-et-al-CDD-142-246-252-2017.pdf

http://benthamscience.com/journals/current-drug-delivery/volume/14/issue/2/page/246/},

doi = {10.2174/1567201813666160512150710},

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 = {246 - 252},

abstract = {Background. Short interfering RNAs (siRNAs) are double-stranded RNA molecules able to specifically targeting genes products responsible for human diseases. Cyclin D1 (CyD1) is a cell cycle-regulatory molecule, up-regulated at sites of inflammation in several tissues. CyD1 is a very interesting potential target in lung and colon inflammatory diseases.

Objective. The aim of this paper was testing CyD1 expression in human lung and colon tissues after the application of an inflammatory stimulus, and verifying its gene silencing by using siRNA for CyD1 (siCyD1). 

Method. Colon and pulmonary biopsies were treated with siCyD1 by using two different transfection carriers: a) invivofectamine and b) ad hoc produced nanoliposomes. After 24 hours of incubation with nanoliposomes encapsulating siRNA or invivofectamine-CyD1siRNA, in presence or absence of EC-LPS, we analysed the protein expression of CyD1 through Western-Blotting. 

Results. After EC-LPS treatment, in both colon and pulmonary biopsies, an overexpression of CyD1was found (about 64% and 40% respectively). Invivofectamine-CyD1 siRNA reduced the expression of CyD1 approximately by 46% compared to the basal condition, and by around 65% compared to EC-LPS treated colon samples. In lung, following invivofectamine siRNA silencing in the presence of EC-LPS, no reduction was observed. 

Ad hoc nanoliposomes were able to enter colon and lung tissues, but CyD1 silencing was reported in 2 colon samples out of 4 and no efficacy was demonstrated in the only lung sample we studied.

Conclusion. It is possible to silencing Cyclin D1 expression in vitro “organ culture” model. Our preliminary results encourage further investigations, using different siRNA concentrations delivered by nanoliposomes.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{D'Apolito2016,

title = {Microfluidic investigation of the effect of liposome surface charge on drug delivery in microcirculation},

author = {Rosa D'Apolito and Sabrina Bochicchio and Annalisa Dalmoro and Anna Angela Barba and Stefano Guido and Giovanna Tomaiuolo},

url = {https://www.gruppotpp.it/wp-content/uploads/2017/03/08.-DApolito-et-al-CDD-142-231-238-2017.pdf

http://benthamscience.com/journals/current-drug-delivery/volume/14/issue/2/page/231/},

doi = {10.2174/1567201813666160813172047},

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 = {231 - 238},

abstract = {Nano-carrier drug transport in blood microcirculation is one of the hotspots of current research in drug development due to many advantages over traditional therapies, such as reduced side-effects, target delivery, controlled release, improved pharmacokinetics and therapeutic index. Despite the substantial efforts made in the design of nanotherapeutics, the big majority of the used strategies failed to overcome the biological barriers to drug transport encountered in human microvasculature, such as transport by blood flow via the microcirculatory network and margination, the mechanism according to which particles migrate along vessel radius to the wall. In fact, drug transport efficiency in microvasculature is affected by both the particulate nature of blood and drug carrier properties, such as size, shape and surface charge. 

In this work, the effect of the surface charge of liposomes on their margination in blood flow in microcapillaries was experimentally evaluated. By high-speed video microscopy and image analysis it was found that the two custom-made liposomes (one neuter and the other positively charged) tend to drift laterally, moving towards the wall and accumulating in the cell-free layer. In particular, neuter and cationic liposomes showed a comparable margination propensity, suggesting that the presence of blood cells governs the flow behavior independently on liposome surface charge.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Chiarappa2016,

title = {Chemical Engineering in the “BIO” world},

author = {Gianluca Chiarappa and Mario Grassi and Michela Abrami and Roberto Andrea Abbiati and Anna Angela Barba and Anja Boisen and Valerio Brucato and Giulio Ghersi and Diego Caccavo and Sara Cascone and Sergio Caserta and Nicola Elvassore and Monica Giomo and Stefano Guido and Gaetano Lamberti and Domenico Larobina and Davide Manca and Paolo Marizza and Giovanna Tomaiuolo and Gabriele Grassi },

url = {https://www.gruppotpp.it/wp-content/uploads/2017/03/02.-Chiarappa-et-al-CDD-142-158-178-2017.pdf

http://benthamscience.com/journals/current-drug-delivery/volume/14/issue/2/page/158/},

doi = {10.2174/1567201813666160602230550},

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 = {158 - 178},

abstract = {Modern Chemical Engineering was born around the end of the 19th century in Great Britain, Germany, and the USA, the most industrialized countries at that time. Milton C. Whitaker, in 1914, affirmed that the difference between Chemistry and Chemical Engineering lies in the capability of chemical engineers to transfer laboratory findings to the industrial level. Since then, Chemical Engineering underwent huge transformations determining the detachment from the original Chemistry nest. The beginning of the sixties of the 20th century saw the development of a new branch of Chemical Engineering baptized Biomedical Engineering by Peppas and Langer and that now we can name Biological Engineering. Interestingly, although Biological Engineering focused on completely different topics from Chemical Engineering ones, it resorted to the same theoretical tools such as, for instance, mass, energy and momentum balances. Thus, the birth of Biological Engineering may be considered as a Darwinian evolution of Chemical Engineering similar to that experienced by mammals which, returning to water, used legs and arms to swim. From 1960 on, Biological Engineering underwent a considerable evolution as witnessed by the great variety of topics covered such as hemodialysis, release of synthetic drugs, artificial organs and, more recently, delivery of small interfering RNAs (siRNA). This review, based on the activities developed in the frame of our PRIN 2010-11 (20109PLMH2) project, tries to recount origins and evolution of Chemical Engineering illustrating several examples of recent and successful applications in the biological field. This, in turn, may stimulate the discussion about the Chemical Engineering students curriculum studiorum update.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@article{Dalmoro2016b,

title = { Injectable chitosan/b-glycerophosphate system for sustained release: gelation study, structural investigation and erosion tests},

author = {Annalisa Dalmoro and Michela Abrami and Barbara Galzerano and Sabrina Bochicchio and Anna Angela Barba and Mario Grassi and Domenico Larobina},

url = {https://www.gruppotpp.it/wp-content/uploads/2017/03/06.-Dalmoro-et-al-CDD-142-216-223-2017.pdf



http://benthamscience.com/journals/current-drug-delivery/volume/14/issue/2/page/216/



},

doi = {10.2174/1567201813666160721142202},

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 = {216 - 223},

abstract = {Hydrogels can constitute reliable delivery systems of drugs, including those based on nucleic acids (NABDs) such as small interfering ribonucleic acid (siRNA). Their nature, structure, and response to physiological or external stimuli strongly influence the delivery mechanisms of entrapped active molecules, and, in turns, their possible uses in pharmacological and biomedical applications. In this study a thermo-gelling chitosan/β-glycero-phosphate system has been optimized in order to assess its use as injectable system able to: i) gelling at physiological pH and temperature, and ii) modulate the release of included active ingredients. To this aim we first analyzed the effect of acetic acid concentration on the gelation temperature. We then found the “optimized composition”, namely, the one in which the Tgel is equal to the physiological temperature. The resulting gel was tested, by low field nuclear magnetic resonance (LF-NMR), to evaluate its average mesh-size, which can affect release kinetics of loaded drug. Finally, films of gelled chitosan, loaded with a model drug, have been tested in vitro to monitor their characteristic times, i.e. diffusion and erosion time, when they are exposed to a medium mimicking a physiological environment (buffer solution at pH 7.4). Results display that the optimized system is deemed to be an ideal candidate as injectable gelling material for a sustained release.},

keywords = {Hydrogel Characterization},

pubstate = {published},

tppubtype = {article}

}

@article{Caccavo2016b,

title = {Drug delivery from hydrogels: a general framework for the release modeling},

author = {Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba and Anette Larsson },

url = {https://www.gruppotpp.it/wp-content/uploads/2017/03/03.-Caccavo-et-al-CDD-142-179-189-2017.pdf

http://benthamscience.com/journals/current-drug-delivery/volume/14/issue/2/page/179/},

doi = {10.2174/1567201813666160808102106},

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 = {179 - 189},

abstract = {The controlled delivery of drugs, including siRNAs, can be effectively obtained using Hydrogel-Based Drugs Delivery Systems (HB-DDSs). Successful design of HB-DDSs requires the knowledge of the mechanisms that influence drug release. The modeling of the physical phenomena involved could help in the development and optimization of HB-DDS, sensibly reducing the time and costs required by a trial-and-error procedures. The modeling is rather complex because of the presence of several, synergistic and competing, transport phenomena. In this work a general framework useful for modeling the HB-DDS has been derived and it is proposed, coupling and homogenizing the literature models. It is shown that all of them can be traced back to two different approaches: multiphasic models and multicomponent mixture models. In the first one the hydrogel is seen as constituted by different phases, the behavior of each one being described by their own mass and momentum conservation equations. In the second approach, the hydrogel is considered as made of one phase composed by several components.},

keywords = {Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@article{Cascone2016,

title = {Gastrointestinal behavior and ADME phenomena: I. In vitro simulation},

author = {Sara Cascone and Gaetano Lamberti and Francesco Marra and Giuseppe Titomanlio and Matteo d'Amore and Anna Angela Barba},

url = {https://www.sciencedirect.com/science/article/pii/S1773224716302659

},

doi = {10.1016/j.jddst.2016.08.002},

issn = {1773-2247},

year  = {2016},

date = {2016-10-01},

journal = {Journal of Drug Delivery Science and Technology},

volume = {35},

pages = {272-283},

abstract = {The most common administration route for pharmaceuticals is the oral one. A drug orally administered has to undergo several processes in order to carry out its therapeutic potential. The pharmaceutical has to dissolve and to release the API (Active Pharmaceutical Ingredient) in the desired location along the GI (Gastro Intestinal) tract, to pass through the intestinal wall, to overcome the liver (first-pass metabolism), and finally to reach the plasma, where it has to be stable during its travel toward the target organ/tissue. The key roles in this complex framework are played by the design (such as matrices, reservoirs, enteric systems) and the testing of the pharmaceuticals.



This review is focused on the state of the art in the pharmaceutical testing methods, carried out by the simulation of what happens once the pharmaceutical has been administered, investigating the in vitro approach. In the first section, the generalities of the dissolution and the ADME (Adsorption, Distribution, Metabolism and Excretion) phenomena are investigated. In the second section, the in vitro apparatuses are described, with a special focus on the role of food in their design and behavior. Some case histories of application for each approach are also discussed.},

keywords = {Biodistribution, In vitro, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@article{Lamberti2016,

title = {Gastrointestinal behavior and ADME phenomena: II. in silico simulation},

author = {Gaetano Lamberti and Sara Cascone and Francesco Marra and Giuseppe Titomanlio and Matteo D'Amore and Anna Angela Barba},

url = {http://www.sciencedirect.com/science/article/pii/S1773224716302118},

doi = {10.1016/j.jddst.2016.06.014},

issn = {1773-2247},

year  = {2016},

date = {2016-07-04},

journal = {Journal of Drug Delivery Science and Technology},

volume = {35},

pages = {165-171},

abstract = {The main goal of the pharmacokinetic modeling is the prediction of the drug concentration in the blood, tissues, and organs. The approaches to the modeling of physiological phenomena can be different on the basis of the details used to describe the Adsorption, Distribution, Metabolism, and Excretion (ADME) phenomena.



This review is focused on the state of the art in the pharmacokinetic modeling, on the different approaches used to describe the drug fate once it is administered. In particular, the early and the recent developments in the pharmacokinetic and in the gastrointestinal behavior modeling are discussed, together with some case histories of their applications.},

keywords = {In silico, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@article{Dalmoro2016b,

title = {In situ coronary stent paving by Pluronic F127\textendashalginate gel blends: formulation and erosion tests},

author = {Annalisa Dalmoro and Anna Angela Barba and Gabriele Grassi and Mario Grassi and Gaetano Lamberti},

url = {http://onlinelibrary.wiley.com/doi/10.1002/jbm.b.33425/abstract;jsessionid=31C6676EE270B6362CB149075EE37B5F.f01t01},

doi = {10.1002/jbm.b.33425},

year  = {2016},

date = {2016-07-01},

journal = {Journal of Biomedical Materials Research Part B: Applied Biomaterials},

volume = {104},

number = {5},

pages = {1013-22},

abstract = {In this work the development of an experimental protocol to perform the in situ gel-paving of coronary stent is presented. Biocompatible aqueous blends of Pluronic F127 and sodium alginates are used as potential drug dosage system for pharmacological in situ treatment of coronary in-stent restenosis. Pluronic F127/alginate aqueous blend has the unique characteristic to be liquid at room condition and to form gel at physiological temperature. The proposed protocol is based on the blend injection on stent wall previously implanted in a flexible silicon pipe mimicking the coronary artery. Injected blend is warmed up until human body temperature achieving a soft gel, then it is reticulated by copper bivalent ions to obtain an hard gel. To test the gel paving resistance to erosion phenomena when it is exposed to fluid flux (i.e. blood flux) a dedicated device, (the Simulated Artery Device, SAD), was built to simulate the human circulatory apparatus. The SAD is an hydraulic circuit in which a buffer solution (at pH 7.4) was fluxed by a peristaltic pump through the pipe hosting the covered stent. Erosion tests were performed monitoring, by gravimetric and spectrophotometric methods, the residual mass anchored to stent mesh after given times. The obtained results showed that the in situ gel-paving developed protocol was efficacious and reliable. The gel-paving was completely eroded in a time of the same order of magnitude of the physiological period required to restore the coronary lesion (subsequent to the atheroma removal) and of a pharmacological therapy to inhibit the in-stent-restenosis pathology. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2015.},

keywords = {coronary stent, drug delivery, erosion phenomena, gel erosion, pluronic/alginate blends},

pubstate = {published},

tppubtype = {article}

}

@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 = {Micro and Nano Vectors},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@article{Caccavo2015b,

title = {Understanding the adhesion phenomena in carbohydrate-hydrogel-based systems: Water up-take, swelling and elastic detachment},

author = { Diego Caccavo and Gaetano Lamberti and Sara Cascone and Anna Angela Barba and Anette Larsson},

url = {http://www.sciencedirect.com/science/article/pii/S0144861715004476},

doi = {10.1016/j.carbpol.2015.05.041},

issn = {01448617},

year  = {2015},

date = {2015-10-01},

journal = {Carbohydrate Polymers},

volume = {131},

pages = {41--49},

abstract = {The bio-adhesion is a complex phenomenon which takes place when two materials (at least one of biological nature, the other usually is a polymeric one) are held together for extended periods of time, usually for local drug delivery purposes. Despite bio-adhesion is widely exploited in commercial pharmaceuticals such as the buccal patches, the underlying phenomena of the process are not completely clarified yet. In this study experimental tests, in which the role of biological membranes is played by a water-rich agarose gel whereas patches are mimicked by hydrogel tablets (made of Carbopol or of Carbopol added with NaCl), have been used to analyze the behavior of the model system above described. Tablets have been forced to adhere on the agarose gel, and after a given contact time they have been detached, recording the required forces. Furthermore weight gain of the tablets (the water transported from the agarose gel toward the tablet) has been quantified. Water transport (during the time in which the contact between tablet and agarose gel is held) and elastic part of mechanical response during the detachment are modelled to achieve a better understanding of the adhesion process. Both the two sub-models nicely reproduce, respectively, the weight gain as well as the swelling of the Carbopol tablets, and the point at which the mechanical response ceases to be purely elastic.},

keywords = {Bio-adhesion, Carbopol, Elastic behavior, Hydrogel Characterization, Hydrogel Modeling, Modeling, Water transport},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@article{Abrahms\'{e}n-Alami2015,

title = {Hydrogel-based drug delivery systems (HB-DDSs): a combined experimental-modeling approach},

author = {Susanna Abrahms\'{e}n-Alami and Diego Caccavo and Gaetano Lamberti and Anna Angela Barba and Anna Virid\'{e}n and Anette Larsson},

year  = {2015},

date = {2015-09-01},

journal = {AstraZeneca Internal Journal},

pages = {1-2},

abstract = {In this work, a method based on MR image analysis, already used to quantify the water content in hydrating tablets based on hydrogels, was refined and it was proved to be a powerful source of detailed information: the water contents were obtained as function of position and time for commercial-like tablets based on HPMC, along with the tablets’ shape changes with time, and the drug release kinetics. A mechanistic model, based on transient mass balances and surface deformation due to the hydration and erosion, previously developed and tuned, was thus applied to describe the observed phenomena, giving good results. Both the experimental technique and the mechanistic model have confirmed to be useful tools for the study of the behavior \textendash as well as for the design \textendash of the tablets based on hydrogels.},

keywords = {Hydrogel Characterization, Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@article{Caccavo2015a,

title = {Controlled drug release from hydrogel-based matrices: Experiments and modeling.},

author = { Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba},

url = {http://www.sciencedirect.com/science/article/pii/S0378517315002707},

doi = {10.1016/j.ijpharm.2015.03.054},

issn = {1873-3476},

year  = {2015},

date = {2015-03-01},

journal = {International journal of pharmaceutics},

volume = {486},

number = {1-2},

pages = {144--152},

abstract = {Controlled release by oral administration is mainly achieved by pharmaceuticals based on hydrogels. Once swallowed, a matrix made of hydrogels experiences water up-take, swelling, drug dissolution and diffusion, polymer erosion. The detailed understanding and quantification of such a complex behavior is a mandatory prerequisite to the design of novel pharmaceuticals for controlled oral delivery. In this work, the behavior of hydrogel-based matrices has been investigated by means of several experimental techniques previously pointed out (gravimetric, and based on texture analysis); and then all the observed features were mathematically described using a physical model, defined and recently improved by our research group (based on balance equations, rate equations and swelling predictions). The agreement between the huge set of experimental data and the detailed calculations by the model is good, confirming the validity of both the experimental and the theoretical approaches.},

keywords = {Hydrogel Characterization, Hydrogel Modeling, Hydrogels, Modeling, Texture analysis, Transport phenomena, Water uptake},

pubstate = {published},

tppubtype = {article}

}

@article{Dalmoro2015b,

title = {Qualit\`{a} ed efficienza con l’uso di microonde nel trattamento di alimenti},

author = {Annalisa Dalmoro and Anna Angela Barba and Silvestro Caputo },

url = {https://www.gruppotpp.it/wp-content/uploads/2015/12/dalmoro_et_al_ta_2015.pdf

http://www.interprogettied.com/tecnologie-alimentari-n2-marzo-2015/},

year  = {2015},

date = {2015-03-01},

journal = {Tecnologie Alimentari},

volume = {2},

pages = {32-36},

abstract = {L’obiettivo primario dei processi di sanitizzazione e di trasformazione \`{e} quello di rendere gli alimenti conservabili nel tempo, edibili e pi\`{u} gustosi. Questo scopo non pu\`{o} per\`{o} essere disgiunto da fattori importanti quali il mantenimento del loro patrimonio nutritivo e la sostenibilit\`{a} di processo. Da ci\`{o} l’interesse verso tecnologie pi\`{u} efficaci e allo stesso tempo meno invasive, da applicare per ottenere prodotti alimentari di elevata qualit\`{a}. },

keywords = {Tecnagri},

pubstate = {published},

tppubtype = {article}

}

@article{Caccavo2015c,

title = {Modeling the Drug Release from Hydrogel-Based Matrices},

author = { Diego Caccavo and Sara Cascone and Gaetano Lamberti and Anna Angela Barba},

url = {http://pubs.acs.org/doi/abs/10.1021/mp500563n},

doi = {10.1021/mp500563n},

issn = {1543-8384},

year  = {2015},

date = {2015-02-01},

journal = {Molecular Pharmaceutics},

volume = {12},

number = {2},

pages = {474--483},

publisher = {American Chemical Society},

chapter = {474},

keywords = {Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@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 = {Biopolymer, Drug Delivery Systems, liposome, Micro and Nano Vectors, nucleic acid based drugs},

pubstate = {published},

tppubtype = {article}

}

@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}

}

@article{Dalmoro2015,

title = {Microwave technology applied in post-harvest treatments of cereals and legumes},

author = { Annalisa Dalmoro and Anna Angela Barba and Silvestro Caputo and Francesco Marra and Gaetano Lamberti},

url = {http://www.aidic.it/cet/15/44/003.pdf},

doi = {10.3303/CET1544003},

year  = {2015},

date = {2015-01-01},

journal = {Chemical Engineering Transaction},

volume = {44},

pages = {13--18},

abstract = {For agricultural purposes microwave heating is an emerging technology today successfully applied in postharvest disinfestation treatments of many agricultural products, such as cereals and legumes, susceptible of degradation due to the presence of natural infesting fauna. Microwave irradiation is proposed as an effective alternative to chemical methods of disinfestation which can be characterized by severe side effects. Extensive studies focused on disinfestation treatments assisted by microwave have proved their effectiveness. Overall goal of the present research is to point out correlations between thermo-physic properties and irradiation conditions (power, time to exposure, load configuration) to stabilize cereals and legumes in short time without damages of structures and nutritive features. In this work, two kinds of agro-foods, weak wheat and beans, were undergone to microwave heating and several physical properties, devoted to control structural possible changes, were investigated on irradiated samples. The achieved results show that the applied irradiation protocol globally does not affect water uptake phenomena in swelling and cooking treatments, peel hardness and germination capability of seeds.},

keywords = {Tecnagri},

pubstate = {published},

tppubtype = {article}

}

@article{Caccavo2015,

title = {Hydrogel-based Granular Phytostrengtheners for Prolonged Release: Production and Characterization},

author = { Diego Caccavo and Sara Cascone and Maria Chiara Amoroso and Pietro Apicella and Gaetano Lamberti and Anna Angela Barba},

url = {http://www.aidic.it/cet/15/44/040.pdf},

doi = {10.3303/CET1544040},

year  = {2015},

date = {2015-01-01},

journal = {Chemical Engineering Transaction},

volume = {44},

pages = {235--240},

abstract = {Soil wellness is an indispensable requirement to obtain fruits and vegetables with finest quality and with high yields. To the purpose, periodical administrations of nutrients, as well as phytostrengtheners could be required. Crucial goals to maximize the economic and environmental sustainability of the whole cultivation are the decrease of the dosages number together with the increase of the active substance availability within the soil. With these aims a controlled release phytostrengtheners encapsulated in a granular Hydroxypropyl methylcellulose matrix has been developed exploiting the wet granulation process. The granular product has been analyzed in terms of Particle Size Distribution (PSD), morphology and flowability. The results showed the effectiveness of the granulation process and the good flowability of the granules, highly desirable features for the product handling and commercialization.},

keywords = {Granulation, Hydrogel Characterization, Tecnagri},

pubstate = {published},

tppubtype = {article}

}

@article{Cascone2015,

title = {Optimization of Chelates Production Process for Agricultural Administration of Inorganic Micronutrients},

author = { Sara Cascone and Pietro Apicella and Diego Caccavo and Gaetano Lamberti and Anna Angela Barba},

url = {http://www.aidic.it/cet/15/44/037.pdf},

doi = {10.3303/CET1544037},

year  = {2015},

date = {2015-01-01},

journal = {Chemical Engineering Transaction},

volume = {44},

pages = {217--222},

abstract = {The iron chlorosis is one of the most diffused plant disease, which affects their growth and reduces the yield of harvests. This disease is caused by the iron deficiency and it is highlighted by the progressive yellowing of plants due to the reduction of chlorophyll production. The most efficient and diffused therapy against the iron chlorosis is the use of chelating agents and, among them, the o,o-EDDHA/Fe3+, the most stable isomer of EDDHA, is the most used due to its capacity to guarantee a prolonged treatment. The aim of this work is to develop a production process environment friendly, based on the recovering and recycling of organic solvents to minimize the waste produced. The feed organic solvents ratio has been varied evaluating the synthesis yield and the percentage of o,o-EDDHA/Fe3+ produced to identify the best feeding conditions. Several products have been then tested on lettuce plants to determine their usability.},

keywords = {Chelating Agents, Tecnagri},

pubstate = {published},

tppubtype = {article}

}

@article{Abbiati2015a,

title = {A PSE approach to patient-individualized physiologically-based pharmacokinetic modeling},

author = { Roberto Andrea Abbiati and Gaetano Lamberti and Anna Angela Barba and Mario Grassi and Davide Manca},

url = {http://www.sciencedirect.com/science/article/pii/B9780444635785500104},

doi = {10.1016/B978-0-444-63578-5.50010-4},

issn = {15707946},

year  = {2015},

date = {2015-01-01},

journal = {12th International Symposium on Process Systems Engineering and 25th European Symposium on Computer Aided Process Engineering},

volume = {37},

pages = {77--84},

publisher = {Elsevier},

series = {Computer Aided Chemical Engineering},

abstract = {Pharmacokinetic modeling allows predicting the drug concentration reached in the blood as a consequence of a specific administration. When such models are based on mammalian anatomy and physiology it is possible to theoretically evaluate the drug concentration in every organ and tissue of the body. This is the case of the so-called physiologically based pharmacokinetic (PBPK) models. This paper proposes and validates a procedure to deploy PBPK models based on a simplified, although highly consistent with human anatomy and physiology, approach. The article aims at reducing the pharmacokinetic variations among subjects due to inter-individual variability, by applying a strategy to individualize some model parameters. The simulation results are validated respect to experimental data on remifentanil.},

keywords = {Complexity reduction, In silico, Lumping, Personalization, Pharmacokinetics, Physiologically-Based modeling, Remifentanil},

pubstate = {published},

tppubtype = {article}

}

@article{Dalmoro2014a,

title = {Random l-lactide/$epsilon$-caprolactone copolymers as drug delivery materials},

author = { Annalisa Dalmoro and Anna Angela Barba and Marina Lamberti and Mina Mazzeo and Vincenzo Venditto and Gaetano Lamberti},

url = {http://link.springer.com/10.1007/s10853-014-8317-x},

doi = {10.1007/s10853-014-8317-x},

issn = {0022-2461},

year  = {2014},

date = {2014-09-01},

journal = {Journal of Materials Science},

volume = {49},

number = {17},

pages = {5986--5996},

publisher = {Springer US},

abstract = {In this work, the degradation phenomena and the release kinetics of an active molecule from matrices systems made of random copolymers of $epsilon$-caprolactone (CL) and l-lactide (LA) were investigated by exposing the matrices, shaped as thin films, to simulated physiological environments. $alpha$-tocopherol was incorporated into the films as hydrophobic model molecule with the aim to investigate both its release pattern and its effect on erosion phenomena. In particular, the films have been kept at controlled conditions (temperature, stirring, pH) and they were characterized in terms of weight loss, water uptake, thermal properties, and change of number average molecular weight, in order to explain the molecule release kinetics and the degradation pathways of the copolymers. The main findings of this study are that the erosion phenomena take place significantly only when a critical value of the molecular mass was obtained in the sample; that the presence of the drug stabilizes the matrix and it decreases the rate of molecular mass decrease; and that crystallinity, reducing the chain mobility, causes lower erosion rates.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{del2014physiologically,

title = {A physiologically oriented mathematical model for the description of in vivo drug release and absorption},

author = {Renzo {Del Cont} and Michela Abrami and Dritan Hasa and Beatrice Perissutti and Dario Voinovich and Anna Angela Barba and Gaetano Lamberti and Gabriele Grassi and Italo Colombo and Davide Manca and Mario Grassi},

url = {http://pub.iapchem.org/ojs/index.php/admet/article/view/34},

doi = {10.5599/admet.2.2.34},

issn = {1848-7718},

year  = {2014},

date = {2014-07-01},

journal = {ADMET \& DMPK},

volume = {2},

number = {2},

pages = {80--97},

abstract = {This paper focuses on a physiologically-oriented mathematical model aimed at studying the in vivo drug release, absorption, distribution, metabolism and elimination (ADME). To this purpose, the model accounts for drug delivery from an ensemble of non-eroding poly-disperse polymeric particles and the subsequent ADME processes. The model outcomes are studied with reference to three widely used drugs: theophylline, temazepam and nimesulide. One of the most important results of this study is the quantitative evaluation of the interplay between the release kinetics and the subsequent ADME processes. Indeed, it is usually assumed that in vivo drug release coincides with in vitro so that the effect exerted by the ADME processes is neglected. In addition, the proposed model may be an important tool for the design of delivery systems since, through proper changes, it could also account for different oral delivery systems.},

keywords = {In silico, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}