@article{Piano}2024,

title = {Drug release from hydrogel-based matrix systems partially coated: experiments and modeling},

author = {Raffaella {De Piano} and Diego Caccavo and Sara Cascone and Caterina Festa and Gaetano Lamberti and Anna Angela Barba },

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85092403044\&doi=10.1016%2fj.jddst.2020.102146\&partnerID=40\&md5=e519d84642480478a063b4c7b4e2832e},

doi = {10.1016/j.jddst.2020.102146},

isbn = {17732247},

year  = {2024},

date = {2024-05-01},

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

volume = {61},

number = {102146},

abstract = {Hydrogel-based matrix systems are largely used as controlled drug delivery systems, since it is possible to get the desired drug release profile properly designing the system in term of composition, drug loading and shape. Meanwhile, the mathematical modeling of the phenomena involved in the drug release process is a useful tool to understand and to predict the complex behavior of these systems, in term of water up-take, matrix swelling and erosion, drug diffusion and release. Furthermore, the coating of the matrix is used to provide certain characteristics such as enteric resistance, meanwhile making more complex the mathematical description of the process. In this work cylindrical tablets made of hydroxyl-propyl-methyl-cellulose (HPMC) loaded with theophylline (TP), as obtained or coated by an impermeable painting on the lateral surface were dissolved in a USP II apparatus, and the release of TP, as well as of HPMC and the shape changes were monitored in time, for several rotational speeds of the impeller. The experimental data gathered were used to tune a previously proposed mathematical model. The model was found able to correctly describe all the observed phenomena, confirming its usefulness as a tool in design and production of pharmaceutics.},

keywords = {drug release, Modeling, Tablets, Theophylline},

pubstate = {published},

tppubtype = {article}

}

@article{Caccavo2024,

title = {Analysis and simulation of wet-granulation processes},

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

url = {https://doi.org/10.1016/j.jtice.2024.105455},

year  = {2024},

date = {2024-03-22},

journal = {Journal of the Taiwan Institute of Chemical Engineers},

volume = {159},

number = {105455},

abstract = {Size enlargement by wet-granulation is one of the most important unit operation in several industrial fields: pharmaceutics, food processing, animal nutrition, agronomics, and so on. A lot of techniques have been used in order to measure the particle size distributions (PSD) and a few different approaches are available to model the PSD evolution during the process, mainly based on population balance equations (PBE). However, difficulties in both the activities (reliable measurement and robust modeling) have hindered their diffusion in industrial practice, keeping the granulation closer to an art than to a science.},

keywords = {Dynamic image analysis, Modeling, Particle size distribution, Population balance equation, Wet-granulation},

pubstate = {published},

tppubtype = {article}

}

@article{Caccavo2024b,

title = {Impact of drug release in USP II and in-vitro stomach on pharmacokinetic: The case study of immediate-release carbamazepine tablets},

author = {Diego Caccavo and Marco Iannone and Anna Angela Barba and Gaetano Lamberti},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85145821046\&doi=10.1016%2fj.ces.2022.118371\&partnerID=40\&md5=d837f63862ad2ca8881845352400e79a},

doi = {10.1016/j.ces.2022.118371},

issn = {92509},

year  = {2024},

date = {2024-03-05},

journal = {Chemical Engineering Science},

volume = {267},

number = {118371},

abstract = {The in-vitro reproduction of the real physiological conditions that occur along the gastrointestinal (GI) tract would be the optimum for the dissolution and release testing of pharmaceutical formulations for oral intake. In this study a method for the automated reproduction of the real pH conditions that occurs in the gastric cavity and a device that mimics the same forces exerted by the internal walls of the stomach are presented. Commercial immediate-release carbamazepine tablets were tested in conventional (USP II) and unconventional apparatuses. The gastric pH and the fluid dynamic conditions are factors to be carefully considered since they both affect the drug release profiles. Finally, a PBPK model was used to predict the evolution of plasma drug concentrations knowing the experimental in-vitro GI release behavior. It was found that, for immediate-release carbamazepine tablet, the gastric drug release does not have a major impact on the plasmatic drug concentration.},

keywords = {case study, drug release, in-vitro stomach},

pubstate = {published},

tppubtype = {article}

}

@article{Apicella2023,

title = {Natural Food Resource Valorization by Microwave Technology: Purslane Stabilization by Dielectric Heating},

author = {Marco Apicella and Giuseppe Amato and {de Bartolomeis, Pietro} and Anna Angela Barba and Vincenzo {De Feo}},

url = { https://doi.org/10.3390/foods12234247 },

doi = {10.3390/foods12234247},

year  = {2023},

date = {2023-11-24},

journal = {Foods },

volume = {12(23)},

number = {4247},

abstract = {The application of microwave-assisted drying is a promising technique due to the features of process sustainability that are usable for responsible productions. It is largely applied for the stabilization of food products, especially in the agro-food sector. In this study, the weed Portulaca oleracea L. (purslane), with its richness in antioxidant components in addition to its recognized pharmacological properties, has been considered due to its potential to be a natural, well-accepted future food. Attention was focused on the role of the heat and mass transfer rates involved in the drying processes on the nutritional profile of the dried products. For this purpose, different drying protocols (convective, microwave irradiation, microwave-vacuum irradiation) were applied to different parts of purslane herb (apical, twigs, entire structures) and chemical characterizations were performed by a GC/MS analysis of the extracts of the dried products. The results show that microwave treatments can assure a better preservation of fatty acids such as SFAs, MUFAs, and PUFAs (which constitute over 90% of the total components in the apical part, 65% in twigs, and 85% in microwave-vacuum-dried entire purslane samples) and phytosterols (their highest preservation was found in microwave-dried twigs) compared with convective treatments. The chemical composition variability as well as treatment times depend on the drying rates (in microwave treatments, the times are on a minute scale and the rates are up to three orders of magnitude greater than convective ones), which in turn depend on the heating transport phenomena. This variability can lead towards products that are diversified by properties that transform a weed into a valorized food source.},

keywords = {dielectric heating, fatty acids, food recovery, future food, microwave drying technology, phytosterols, Portulaca oleracea L., valorization},

pubstate = {published},

tppubtype = {article}

}

@article{Mancino2023,

title = {Agarose Cryogels: Production Process Modeling and Structural Characterization },

author = {Raffaele Mancino and Diego Caccavo and Anna Angela Barba and Gaetano Lamberti and Alice Biasin and Angelo Cortesi and Gabriele Grassi and Mario Grassi and Michela Abrami},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85172281028\&doi=10.3390%2fgels9090765\&partnerID=40\&md5=7753d30977c1b97694c4ede138749d57},

doi = {10.3390/gels9090765},

issn = {23102861},

year  = {2023},

date = {2023-09-20},

journal = {Gels},

volume = {9},

number = {9},

pages = {765},

abstract = {A cryogel is a cross-linked polymer network with different properties that are determined by its manufacturing technique. The formation of a cryogel occurs at low temperatures and results in a porous structure whose pore size is affected by thermal conditions. The adjustable pore sizes of cryogels make them attractive for diverse applications. In this study, the influence of the external operational temperature, which affects the cooling and freezing rates, on the production of cryogels with 2% w/w agarose is investigated. Moreover, a mathematical model is developed to simulate the cryogel production process and provide an initial estimate of the pore size within the structure. The predictions of the model, supported by qualitative light microscopy images, demonstrate that cryogels produced at higher process temperatures exhibit larger pore sizes. Moreover, the existence of pore size distribution within the gel structure is confirmed. Finally, stress relaxation tests, coupled with an image analysis, validates that cryogels produced at lower temperatures possess a higher stiffness and slower water release rates.},

keywords = {Agarose, cryogels, Equilibrium, Hydrogels, Modeling, Rheology},

pubstate = {published},

tppubtype = {article}

}

@article{Piano}2023b,

title = {Polyelectrolyte hydrogels in biological systems: Modeling of swelling and deswelling behavior},

author = {Raffaella {De Piano} and Diego Caccavo and Anna Angela Barba and Gaetano Lamberti},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85161532217\&doi=10.1016%2fj.ces.2023.118959\&partnerID=40\&md5=a269515dd96617e9242f75711516e847},

doi = {10.1016/j.ces.2023.118959},

issn = {00092509},

year  = {2023},

date = {2023-09-05},

journal = {Chemical Engineering Science},

volume = {279},

number = {118959},

abstract = {Polyelectrolyte hydrogels are a particular class of hydrogel whose behavior is connected to the variation of pH in the surrounding solution. Their behavior is influenced by the ionizable groups present on their chain. These groups could be acid or basic and polyelectrolytes could be anionic or cationic. To fully understand their behavior mathematical modeling has been widely used over many years. In this work a model based on a monophasic approach will be used to describe a general behavior of anionic hydrogels in a steady state condition at pH lower (or equal) to seven. Free swelling experiments and constrained swelling experiments have been simulated varying the parameters of the model to highlight the properties of the material. From a comparison with experimental data, it results that the proposed model can describe the general behavior of the system as described in the literature.},

keywords = {Biological systems, Equilibrium, Hydrogels, Modeling, Polyelectrolytes},

pubstate = {published},

tppubtype = {article}

}

@article{Piano}2023,

title = {Hydrogel: pH Role on Polyelectrolyte Behaviour in Aqueous Media},

author = {Raffaella {De Piano} and Diego Caccavo and Anna Angela Barba and Gaetano Lamberti},

doi = {10.3303/CET23100067},

issn = {22839216},

year  = {2023},

date = {2023-06-30},

journal = {Chemical Engineering Transactions},

volume = {100},

pages = {397-402},

abstract = {Polyelectrolytes are a class of polymer whose swelling depends on the external condition of pH. The dissociation of the ionizable groups is strongly depended on the concentration of the H+ ions in solution and this leads to different swelling behaviour changing the external pH. Since these materials are versatile and used in various fields, an in-depth knowledge of their behaviour becomes important to use them appropriately. The present work aims to offer an overview of the behaviour of these materials in solution through an experimental and a steady state modelling part. The results serve as a fundamental basis to understand the behaviour of these systems, including transient periods, leading to a comprehensive and predictable description.},

keywords = {Hydrogel, Polyelectrolyte Behaviour},

pubstate = {published},

tppubtype = {article}

}

@article{Caccavo2023b,

title = {Coaxial Injection Mixer for the Continuous Production of Nanoparticles},

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

url = {https://doi.org/10.3303/CET23100051},

doi = {10.3303/CET23100051},

issn = {22839216},

year  = {2023},

date = {2023-06-30},

journal = {Chemical Engineering Transactions},

volume = {100},

pages = {Pages 301-306},

abstract = {Nanoparticles (NPs) production in batch reactors is limited in terms of reproducibility and control over physical properties such as particle size. Microfluidic techniques and flow-focusing can improve these limitations, but continuous nanoprecipitation through turbulent mixing can also be achieved. This study evaluates the effect of fluid dynamics on NP production and characteristics in a coaxial jet mixer. The results showed that the vertical and horizontal configurations of the mixer impact mixing performance, with buoyancy in the horizontal configuration causing fluid segregation and altering the coaxiality. The mixing performance was tested using water/water and ethanol/water systems with different flow rates, and results indicated that a turbulent jet develops at high values of both the Flow Momentum Ratio (FMR) and Reynolds number (NRe). The mixing time for the turbulent jet was found to have a clear relationship with the Reynolds number and FMR and was successfully fitted using a power law equation. Finally, the results showed that the NPs produced in turbulence were smaller and more uniform in size, with a Z-average half that of those produced in laminar conditions. The improved size uniformity and reduced dimensions of the particles resulted in a clearer final product. This study suggests that micromixing is a more favourable method for producing liposomes with improved characteristics and higher productivity compared to interdiffusion.},

keywords = {Coaxial Injection, Continuous Production, nanoparticles},

pubstate = {published},

tppubtype = {article}

}

@article{Caccavo2023,

title = {Impact of drug release in USP II and in-vitro stomach on pharmacokinetic: The case study of immediate-release carbamazepine tablets},

author = {Diego Caccavo and Marco Iannone and Anna Angela Barba and Gaetano Lamberti},

url = {https://www.sciencedirect.com/science/article/pii/S0009250922009563},

doi = {10.1016/j.ces.2022.118371},

year  = {2023},

date = {2023-03-05},

journal = {Chemical Engineering Science},

volume = {267},

abstract = {The in-vitro reproduction of the real physiological conditions that occur along the gastrointestinal (GI) tract would be the optimum for the dissolution and release testing of pharmaceutical formulations for oral intake. In this study a method for the automated reproduction of the real pH conditions that occurs in the gastric cavity and a device that mimics the same forces exerted by the internal walls of the stomach are presented. Commercial immediate-release carbamazepine tablets were tested in conventional (USP II) and unconventional apparatuses. The gastric pH and the fluid dynamic conditions are factors to be carefully considered since they both affect the drug release profiles. Finally, a PBPK model was used to predict the evolution of plasma drug concentrations knowing the experimental in-vitro GI release behavior. It was found that, for immediate-release carbamazepine tablet, the gastric drug release does not have a major impact on the plasmatic drug concentration.},

keywords = {Drug Delivery Systems, Mathematical modeling, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@article{Terghini2022,

title = {Solution of the population balance equation for wet granulation using second kind Chebyshev polynomials},

author = {Ibtissem Terghini and Abdelmalek Hasseine and Diego Caccavo and Hans J\"{o}rg Bart},

url = {https://doi.org/10.1016/j.cherd.2022.11.028},

doi = {10.1016/j.cherd.2022.11.028},

issn = {02638762},

year  = {2022},

date = {2022-12-01},

journal = {Chemical Engineering Research and Design},

volume = {189},

pages = {262-271},

abstract = {Wet granulation is used in many industrial fields, such as pharmaceutical and nutraceutical, to improve compressibility properties of powders. The comprehension of the physical phenomena of the granulation process, such as simultaneous particle breakage, aggregation, and nucleation, is fundamental to optimize the operating conditions. In this work the population balance equation (PBE), used to mathematically describe these physical phenomena, has been numerical solved with a new finite element method with expansion coefficients in terms of a truncated series expansion with the orthogonal second kind Chebyshev basis polynomials. Such a numerical method is a straightforward and effective method, which has the advantage of concurrently giving the distribution and the different required moments. Moreover, the proposed model accounting for the breakage, aggregation, and nucleation phenomena was used in an ad-hoc optimization procedure to describe the particle size distribution of experimental results of a wet granulation process reaching satisfactorily RMS values. },

keywords = {Inverse problem, Orthogonal Chebyshev basis polynomials, Population balance modelling, Wet granulation},

pubstate = {published},

tppubtype = {article}

}

@article{Iannone2022b,

title = {A low-cost push\textendashpull syringe pump for continuous flow applications},

author = {Marco Iannone and Diego Caccavo and Anna Angela Barba and Gaetano Lamberti},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85126485889\&doi=10.1016%2fj.ohx.2022.e00295\&partnerID=40\&md5=dc11ca55d5dc7a36fb1415ec58406b11},

doi = {10.1016/j.ohx.2022.e00295},

issn = {24680672},

year  = {2022},

date = {2022-04-11},

journal = {HardwareX},

volume = {11},

number = {e00295},

abstract = {Syringe pumps are very useful tools to ensure a constant and pulsation-free flow rate, however usability is limited to batch processes. This article shows an open-source method for manufacturing a push pull syringe pump, valid for continuous processes, easy to build, low-cost and programmable. The push-pull syringe pump (PPSP) is driven by an Arduino nano ATmega328P which controls a NEMA 17 in microstepping via the A4988 stepper driver. The Push-Pull Syringe Pump setup is configurable by means of a digital encoder and an oled screen programmed using C ++. A PCB was designed and built to facilitate the assembly of the device. The continuous flow is guaranteed by four non-return valves and a dampener, which has been sized and optimized for use on this device. Finally, tests were carried out to evaluate the flow rates and the linearity of the flow. The device is achievable with a cost of less than 100 €. },

keywords = {3D-printing, Continuous flow, Dual syringe pump, Push\textendashpull},

pubstate = {published},

tppubtype = {article}

}

@article{Martino}2022,

title = {Postharvest Microwave Drying of Basil (Ocimum basilicum L.): The Influence of Treatments on the Quality of Dried Products},

author = {Laura {De Martino} and Lucia Caputo and Giuseppe Amato and Marco Iannone and Anna Angela Barba and Vincenzo {De Feo}},

url = {https://www.scopus.com/record/display.uri?eid=2-s2.0-85128079847\&doi=10.3390%2ffoods11071029\&origin=inward\&txGid=638d510cd273b4bd45db2f3643c30b49},

doi = {10.3390/foods11071029},

isbn = {23048158},

year  = {2022},

date = {2022-04-01},

journal = {Foods},

volume = {11},

number = {1029},

abstract = {Edible herbs are widely used in the human diet due to their pleasant flavors and countless health benefits associated with their components having, mainly, antioxidant and anti-inflammatory therapeutic functions. Since herbs are highly perishable materials because of their high water content, to guarantee products are safe and stable over time, it is necessary that they undergo stabilization operations. The application of microwave-assisted drying, a promising technique in terms of process sustainability, for the stabilization of the aromatic herb, Ocimum basilicum L., was investigated. The activities were carried out by applying different operating conditions in order to evaluate the impact of the time/temperature combination on the final quality of dried basil. The latter was investigated via the chemical characterization of extracted essential oils and tissue damages. Conventional convective processes were also applied to perform comparisons between dried basil products both under production and the quality preservation points of view. Results showed that microwave heating is suitable as a drying method, as expected, due to the well-known interaction between vegetable tissue (rich in water) and the electromagnetic field; and that drying methods have a different influence on the chemical composition of the essential oils extracted from dried products, in terms of the number (ranging from 41 to 18 components in different dried samples) and percentage (until 67% in linalool and 21% in α-trans-bergamotene in different dried samples) of its’ constituents. },

keywords = {drying methods, essential oil, microwave heating, Ocimum basilicum L, process sustainability},

pubstate = {published},

tppubtype = {article}

}

@article{Iannone2022,

title = {A low-cost push\textendashpull syringe pump for continuous flow applications},

author = {Marco Iannone and Diego Caccavo and Anna Angela Barba and Gaetano Lamberti},

url = {https://www.sciencedirect.com/science/article/pii/S2468067222000402},

doi = {10.1016/j.ohx.2022.e00295},

year  = {2022},

date = {2022-04-01},

journal = {HardwareX},

volume = {11},

abstract = {Syringe pumps are very useful tools to ensure a constant and pulsation-free flow rate, however usability is limited to batch processes. This article shows an open-source method for manufacturing a push pull syringe pump, valid for continuous processes, easy to build, low-cost and programmable.



The push\textendashpull syringe pump (PPSP) is driven by an Arduino nano ATmega328P which controls a NEMA 17 in microstepping via the A4988 stepper driver. The Push-Pull Syringe Pump setup is configurable by means of a digital encoder and an oled screen programmed using C ++. A PCB was designed and built to facilitate the assembly of the device. The continuous flow is guaranteed by four non-return valves and a dampener, which has been sized and optimized for use on this device. Finally, tests were carried out to evaluate the flow rates and the linearity of the flow. The device is achievable with a cost of less than 100 €.},

keywords = {Instrumentation and control, New devices, Prototyping},

pubstate = {published},

tppubtype = {article}

}

@article{Yu2021,

title = {Gelation process of carboxymethyl chitosan-zinc supramolecular hydrogel studied with fluorescence imaging and mathematical modelling},

author = {Xu-Dong Yu and Jia-Hui Li and Heng Li and Ju Huang and Diego Caccavo and Gaetano Lamberti and Li-Qiang Chu },

url = {https://www.sciencedirect.com/science/article/pii/S0378517321006098},

doi = {10.1016/j.ijpharm.2021.120804},

isbn = {218995},

year  = {2021},

date = {2021-06-16},

journal = {International Journal of Pharmaceutics},

volume = {605},

number = {120804},

abstract = {Herein we report on a detailed study about the gelation kinetics of carboxymethyl chitosan-zinc (CMCh-Zn) supramolecular hydrogel by taking advantage of its intrinsic fluorescence property. A specific gelation device is designed and the gel front can be directly visualized under 365 nm UV light. The results show that when increasing Zn2+ concentration from 0.1 M to 1.0 M, the apparent diffusion coefficient increases gradually from 2.72×10-6 cm2/s to 4.50×10-6 cm2/s. The gelation kinetics then is described with a “zero order” mathematical model, proving that the gel thickness is related to the square root of the gelation time and the diffusion step is the controlling step of the gelation process. Later a more advanced model, developed in 1D geometry and solved numerically, is used to describe and predict experimental results, proving its reliability and the correct description of all the phenomena involved in the gelation process of CMCh-Zn hydrogel.},

keywords = {Hydrogel Characterization, Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@article{Caccavo2021,

title = {Dynamometric measurements of hydrogels' mechanical spectra},

author = {Diego Caccavo and Rosario Cavallo and Michela Abrami and Mario Grassi and Anna Angela Barba and Gaetano Lamberti},

url = {https://onlinelibrary.wiley.com/doi/full/10.1002/app.50702},

doi = {10.1002/app.50702},

year  = {2021},

date = {2021-03-12},

journal = {Journal of Applied Polymer Science},

volume = {138},

number = {50702},

abstract = {Hydrogels' viscoelastic behavior is crucial in several applications and an in‐depth knowledge and characterization of this property is essential to select the most appropriate gel for the specific use. Oscillatory shear measurements are the most commonly used techniques to perform the viscoelastic characterization of hydrogels, among other materials, and it is performed mainly by using plate‐plate shear rheometers. Despite these instruments constitute one of the best options to analyze the mechanical response of materials, they are quite expensive and require well trained operators, which confine their presence exclusively in engineering labs. However, the use of hydrogels brought these materials to be present in countless sectors, and therefore poses the need of reliable characterization with as much simple and common instrumentations. Therefore, aim of this work is to present the possibility to obtain a trustworthy characterization of the viscoelasticity of hydrogel by using a Texture Analyzer set to work with sinusoidal deformations.},

keywords = {Gels, Rheology, Viscosity and Viscoelasticity},

pubstate = {published},

tppubtype = {article}

}

@article{Piano}2020,

title = {Drug release from hydrogel-based matrix systems partially coated: experiments and modeling},

author = {Raffaella {De Piano} and Diego Caccavo and Sara Cascone and Caterina Festa and Gaetano Lamberti and Anna Angela Barba},

url = {https://www.sciencedirect.com/science/article/abs/pii/S1773224720314350?via%3Dihub},

doi = {10.1016/j.jddst.2020.102146},

year  = {2020},

date = {2020-10-07},

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

abstract = {Hydrogel-based matrix systems are largely used as controlled drug delivery systems, since it is possible to get the desired drug release profile properly designing the system in term of composition, drug loading and shape. Meanwhile, the mathematical modeling of the phenomena involved in the drug release process is a useful tool to understand and to predict the complex behavior of these systems, in term of water up-take, matrix swelling and erosion, drug diffusion and release. Furthermore, the coating of the matrix is used to provide certain characteristics such as enteric resistance, meanwhile making more complex the mathematical description of the process. In this work cylindrical tablets made of hydroxyl-propyl-methyl-cellulose (HPMC) loaded with theophylline (TP), as obtained or coated by an impermeable painting on the lateral surface were dissolved in a USP II apparatus, and the release of TP, as well as of HPMC and the shape changes were monitored in time, for several rotational speeds of the impeller. The experimental data gathered were used to tune a previously proposed mathematical model. The model was found able to correctly describe all the observed phenomena, confirming its usefulness as a tool in design and production of pharmaceutics.},

keywords = {drug release, Modeling, Tablets, Theophylline},

pubstate = {published},

tppubtype = {article}

}

@article{Simone}2020b,

title = {Nanoliposomes in polymeric granules: Novel process strategy to produce stable and versatile delivery systems},

author = {Veronica {De Simone} and Annalisa Dalmoro and Sabrina Bochicchio and Diego Caccavo and Gaetano Lamberti and Paolo Bertoncin and Anna Angela Barba},

url = {https://www.sciencedirect.com/science/article/abs/pii/S1773224720311679?via%3Dihub},

doi = {10.1016/j.jddst.2020.101878},

year  = {2020},

date = {2020-07-09},

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

volume = {59},

pages = {7},

abstract = {Liposomes, due to their mimetic cellular composition, are gaining great attention as release systems for lipophilic and hydrophilic molecules. However, liposomes can present a high tendency to degrade and aggregate into biological fluids and under storage conditions. To overcome these limitations, in this work, a stabilizing strategy consisting in liposomes incorporation into polymeric granules was studied. Wet granulation was adopted to produce granules of hydroxypropyl methylcellulose (HPMC) and liposomal suspensions were used as the binder phase. In particular, in this study, three different percentages of liposome load in HPMC granules were investigated (1%, 5% and 10% w/w) focusing the attention on several relevant technological characteristics of the achieved solid particulates: size, flow index, mechanical strength (granules without liposomal inclusions were used as a control). Morphological observations (by TEM) confirmed the presence of intact liposomes in dry HPMC granules; moreover, it was found that the binder phase with the lower liposome concentrations (1%, 5%) did not significantly affect size, flowability and hardness of the lipid-polymer granules. Instead, the granules containing the highest percentage of liposomes (10% w/w) have larger dimensions, harder structure and reduced flowability. Therefore, the followed process strategy, under liposomal concentration restrictions, allowed to obtain both the liposomes stabilization, a not trivial technological issue, and the production of particulates with good solid state properties, useful as a versatile dosage form (lipid carriers in polymer carriers).},

keywords = {Compressibility index, Lipid-polymeric, Simil-microfluidic method, Texture analyses, Wet granulation},

pubstate = {published},

tppubtype = {article}

}

@article{Caccavo2020,

title = {Mechanics and drug release from poroviscoelastic hydrogels: Experiments and modeling},

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

url = {https://doi.org/10.1016/j.ejpb.2020.05.020},

doi = {10.1016/j.ejpb.2020.05.020},

year  = {2020},

date = {2020-05-27},

journal = {European Journal of Pharmaceutics and Biopharmaceutics},

volume = {152},

pages = {299-306},

abstract = {Hydrogels are peculiar soft materials formed by a 3D polymeric network surrounded by water molecules. In these systems the mechanical and the chemical energy are well balanced and an applied external stimulus (mechanical or chemical) can cause a distinctive response, where the contributions of the mechanics and the mass transport are combined to form a “poroviscoelastic” behavior. In this work the poroviscoelastic behavior of the agarose gels has been investigated, from the experimental and modeling points of view, by applications of external mechanical stimuli. The pure gel, brought in the non-equilibrium condition, showed that the combined effect of mechanical viscoelasticity and water transport were essential to reach the new equilibrium condition. Furthermore, the agarose gel loaded with a model drug, theophylline, showed that the mechanical stimulus can enhance the drug release from the system by stretching the polymeric chains, modifying the mesh size and therefore the drug diffusion coefficient.},

keywords = {Agarose, drug delivery, Hydrogels, Modeling, Poroviscoelasticity},

pubstate = {published},

tppubtype = {article}

}

@article{Barba2020,

title = {Engineering approaches for drug delivery systems production and characterization},

author = {Anna Angela Barba and Annalisa Dalmoro and Sabrina Bochicchio and Veronica De Simone and Diego Caccavo and Marco Iannone and Gaetano Lamberti},

url = {https://www.sciencedirect.com/science/article/pii/S0378517320302519},

doi = {10.1016/j.ijpharm.2020.119267},

year  = {2020},

date = {2020-03-31},

journal = {International Journal of Pharmaceutics},

abstract = {To find and to test the therapeutic effectiveness (and the limited adverse effects) of a new drug is a long and expensive process. It has been estimated a period of ten years and an expense of the order of one billion USD are required. Meanwhile, even if a promising molecule has been identified, there is the need for operative methods for its delivery. The extreme case is given by gene therapy, in which molecules with tremendous in-vitro efficacy cannot be used in practice because of the lack in useful vector systems to deliver them. Most of the recent efforts in pharmaceutical sciences are focused on the development of novel drug delivery systems (DDSs).

In this review, the work done recently on the development and testing of novel DDSs, with particular emphasis on the results obtained by European research, is summarized. In the first section of the review the DDSs are analyzed accordingly with their scale-size: starting from nano-scale (liposomes, nanoparticles), up to the micro-scale (microparticles), until the macroscopic world is reached (granules, matrix systems). In the following two sections, non-conventional testing methods (mechanical methods and bio-relevant dissolution methods) are presented; at last, the importance of mathematical modeling to describe drug release and related phenomena is reported.},

keywords = {drug delivery, Hydrogel, Innovation in Europe, Microvectors, Modeling, Nanovectors},

pubstate = {published},

tppubtype = {article}

}

@article{Caccavo2019,

title = {An overview on the mathematical modeling of hydrogels’ behavior for drug delivery systems},

author = {Diego Caccavo},

url = {https://www.sciencedirect.com/science/article/pii/S0378517319301188?via%3Dihub},

doi = {10.1016/j.ijpharm.2019.01.076},

year  = {2019},

date = {2019-02-11},

journal = {International Journal of Pharmaceutics},

volume = {560},

pages = {175-190},

abstract = {Hydrogels-based systems (HBSs) for drug delivery are nowadays extensively used and the interest in modeling their behavior is dramatically increasing. In this review a critical overview on the modeling approaches is given, quantitatively and qualitatively analyzing the publications on the subject, the trend of the publications per year and the type of modeling approaches. It was found that, despite the drug release fitting models (i.e. Higuchi’s equation) are the most abundant, their use for HBSs is decreasing in the last years and luckily, considering the limiting assumption on which they were built, they will be confined to simple mathematical fitting equations. Within the mechanistic models the “multi-component” with the swelling approximation (mass transport only) and with the mechanics (fully coupled) are experiencing the highest growth rate, with much more interest toward the last one that, in the next years could be able to provide a first principles model. Statistical models, especially based on the response surface methodology, are rapidly spreading in the scientific community mainly thanks to their ability to be predictive, regardless of the phenomenology, in the analyzed design space with very low efforts. Neural Networks models for HBSs, in countertrend with their use in the pharmaceutical industry, have never take off preferring less data demanding statistical models.},

keywords = {Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@article{Simone}2019,

title = {Effect of binder and load solubility properties on HPMC granules produced by wet granulation process},

author = {Veronica {De Simone} and Annalisa Dalmoro and Gaetano Lamberti and Diego Caccavo and Matteo D'Amore and Anna Angela Barba},

url = {https://www.sciencedirect.com/science/article/pii/S1773224718311043},

doi = {10.1016/j.jddst.2018.12.030},

year  = {2019},

date = {2019-02-01},

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

volume = {49},

pages = {513-520},

abstract = {Hydroxypropyl methylcellulose (HPMC) is one of the most important hydrophilic ingredients used in hydrogel matrices preparation (tablets or granules). In this work, HPMC was used to produce granules loaded with hydrophilic and hydrophobic active molecules to investigate their possible use as release dosage forms for pharmaceutical and nutraceutical applications. Unloaded and vitamins loaded HPMC granules were produced by wet granulation to investigate the effect of molecule solubility and granulation liquid type, on physical, mechanical and release properties. Water-soluble vitamin B12 and water-insoluble vitamin D2 were used as model molecules. Due to their different solubility, two granulation liquid phases were also used: distilled water for granules with B12, and ethanol-water for granules with D2. Results showed that use of ethanol in the liquid phase reduces the granulation yield and produces granules having a less defined shape, a smaller mean size, a less hard structure and a worse flowability. Moreover, ethanol slightly enhances the polymer erosion rate. Results also emphasized that the vitamins solubility does not affect either the physical and the mechanical properties of the produced granules. However, it plays a significant relevant role on the molecule release mechanism, being B12 and D2 were released by diffusion and erosion mechanism, respectively.},

keywords = {Granulation, HPMC},

pubstate = {published},

tppubtype = {article}

}

@article{Simone}2018b,

title = {Wet-granulation process: phenomenological analysis and process parameters optimization},

author = {Veronica {De Simone} and Diego Caccavo and Gaetano Lamberti and Matteo D'Amore and Anna Angela Barba},

url = {https://www.sciencedirect.com/science/article/pii/S0032591018307800},

doi = {10.1016/j.powtec.2018.09.053},

year  = {2018},

date = {2018-12-01},

journal = {Powder Technology},

volume = {340},

pages = {411-419},

abstract = {Wet granulation is a size-enlargement process applied in many industrial fields, such as pharmaceutical, nutraceutical, zootecnichal, to improve flowability and compressibility properties of powders. In this work analysis of the particle size distribution (PSD) of granules was performed to understand the phenomena involved during the granulation process and to optimize the operating conditions. Hydroxypropyl methylcellulose (HPMC) granules were produced spraying distilled water as liquid binder on powders in a low-shear granulator. The experimental campaign was planned using the full factorial design statistical technique varying two factors (impeller rotation speed and binder flow rate), each at three intensities. PSDs of HPMC granules at different granulation times were obtained by an ad hoc dynamic image analysis device based on the free falling particle scheme. PSD measurements showed that wet granules size depends on the simultaneous presence of nucleation, agglomeration and breakage phenomena. The process parameters optimization was carried out using response surface methodology (RSM) and using the granulation yield (% w/w of wet granules within the size range 2000\textendash10,000 μm) as the main variable of interest.},

keywords = {Granulation, HPMC},

pubstate = {published},

tppubtype = {article}

}

@article{Caccavo2018,

title = {Hydrogels: experimental characterization and mathematical modelling of their mechanical and diffusive behaviour},

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

url = {http://pubs.rsc.org/en/content/articlelanding/2018/cs/c7cs00638a#!divAbstract},

doi = {10.1039/C7CS00638A},

issn = {0306-0012},

year  = {2018},

date = {2018-04-07},

journal = {Chemical Society Reviews},

volume = {47},

number = {7},

pages = {2357-2373},

abstract = {Hydrogels are materials widely used in countless applications, particularly in the biomedical, pharmaceutical, and nutraceutical fields, because of their biocompatibility and their mechanical and transport properties. Several approaches are known to evaluate their properties, but only a few approaches are under development to mathematically describe their behaviour, in terms of how the materials answer to mechanical stimuli and how incorporated active substances are released. In this review, the main properties of hydrogels are summarized and the structure\textendashproperty relationships are investigated (i.e. how the macromolecular structure influences the properties of macroscopic samples made of hydrogels). A selection criterion is proposed based on the comparison of three characteristic times: relaxation time, diffusion time, and process time. Then, the most common experimental methods to investigate the hydrogel properties are summarized, along with the state-of-the-art of mathematical modelling, with reference to the mechanical and transport properties of hydrogels, with particular attention to the viscoelastic and poroelastic behaviours. Last but not least, some case histories which can be classified as viscoelastic, poroelastic, or poroviscoelastic behaviours are presented.},

keywords = {Hydrogel Characterization, Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@article{{DeSimone}2018,

title = {HPMC granules by wet granulation process: Effect of vitamin load on physicochemical, mechanical and release properties},

author = {Veronica {De Simone} and Annalisa Dalmoro and Gaetano Lamberti and Diego Caccavo and Matteo D'Amore and Anna Angela Barba },

url = {http://www.sciencedirect.com/science/article/pii/S0144861717313425},

doi = {10.1016/j.carbpol.2017.11.056},

year  = {2018},

date = {2018-02-01},

journal = {Carbohydrate Polymers},

volume = {181},

pages = {939-947},

abstract = {Due to its versatile properties, hydroxypropyl methylcellulose (HPMC) is largely used in many applications and deeply studied in the various  elds such as pharmaceuticals, biomaterials, agriculture, food, water puri cation. In this work, vitamin B12 loaded HPMC granules were produced to investigate their potential application as nutraceutical products. To this aim the impact of vitamin load on physico-chemical, mechanical and release properties of granules, achieved by wet granulation process, was investigated. In particular, three different loads of B12 (1%, 2.3% and 5% w/w) were assayed. Unloaded granules (used as control) and loaded granules were dried, sieved, and then the suitable fraction for practical uses, 0.45\textendash2 mm in size, was fully characterized. Re- sults showed that the vitamin incorporation of 5% reduced the granulation performance in the range size of 0.45\textendash2 mm and led granules with higher porosity, more rigid and less elastic structures compared to unloaded granules and those loaded at 1% and 2.3% of B12. Vitamin release kinetics of fresh and aged granules were roughly found the same trends for all the prepared lots; however, the vitamin B12 was released more slowly when added with a load at 1% w/w, suggesting a better incorporation.},

keywords = {Granulation},

pubstate = {published},

tppubtype = {article}

}

@article{Caccavo2017b,

title = {Modeling the modified drug release from curved shape drug delivery systems - Dome Matrix®},

author = {Diego Caccavo and Anna Angela Barba and Matteo D'Amore and Raffaella {De Piano} and Gaetano Lamberti and Alessandra Rossi and Paolo Colombo},

url = {http://www.sciencedirect.com/science/article/pii/S0939641117308366},

doi = {10.1016/j.ejpb.2017.08.016},

issn = {0939-6411},

year  = {2017},

date = {2017-12-01},

journal = {European Journal of Pharmaceutics and Biopharmaceutics},

volume = {121},

pages = {24-31},

abstract = {The controlled drug release from hydrogel-based drug delivery systems is a topic of large interest for research in pharmacology. The mathematical modeling of the behavior of these systems is a tool of emerging relevance, since the simulations can be of use in the design of novel systems, in particular for complex shaped tablets. In this work a model, previously developed, was applied to complex-shaped oral drug delivery systems based on hydrogels (Dome Matrix®). Furthermore, the model was successfully adopted in the description of drug release from partially accessible Dome Matrix® systems (systems with some surfaces coated). In these simulations, the erosion rate was used as a fitting parameter, and its dependence upon the surface area/volume ratio and upon the local fluid dynamics was discussed. The model parameters were determined by comparison with the drug release profile from a cylindrical tablet, then the model was successfully used for the prediction of the drug release from a Dome Matrix® system, for simple module configuration and for module assembled (void and piled) configurations. It was also demonstrated that, given the same initial S/V ratio, the drug release is independent upon the shape of the tablets but it is only influenced by the S/V evolution. The model reveals itself able to describe the observed phenomena, and thus it can be of use for the design of oral drug delivery systems, even if complex shaped.},

keywords = {Hydrogel Characterization, Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@article{Caccavo2017b,

title = {HPMC-Based Granules for Prolonged Release of Phytostrengtheners in Agriculture},

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

url = {http://www.tandfonline.com/doi/full/10.1080/00986445.2017.1362398},

doi = {10.1080/00986445.2017.1362398 },

issn = {0098-6445},

year  = {2017},

date = {2017-12-01},

journal = {Chemical Engineering Communications},

volume = {204},

number = {12},

pages = {1333-1340},

abstract = {One of the main aim in agriculture is to guarantee soil wellness, which is a fundamental requirement to produce high quality crops with high yields. Focused on this aim, periodical administrations of nutrients or phytostrengtheners are often necessary. The most relevant disadvantages of these administrations are the high dosage number required and the low availability of the substance within the soil. For these reasons, a crucial goal to increase the economic and environmental sustainability of the cultivation process is to reduce the dosage number, which can be obtained increasing the active substance availability in the soil. A granular HPMC (HydroxyPropyl MethylCellulose) matrix, produced using the wet granulation process, was used to encapsulate a phytostrengthener and to guarantee its controlled release. The granular product was characterized in terms of granules properties and phytostrengtheners leaching within the soil. The results showed good flowability and mechanical properties of the granules as well as the possibility to reduce the product leaching with the phytostrengtheners encapsulation in the HPMC matrices.},

keywords = {Granulation, HPMC},

pubstate = {published},

tppubtype = {article}

}

@article{Cascone2017b,

title = {Mimicking the contractions of a human stomach and their effect on pharmaceuticals},

author = {Sara Cascone and Felice {De Santis} and Gaetano Lamberti},

url = {http://www.sciencedirect.com/science/article/pii/S1773224717305907},

doi = {10.1016/j.jddst.2017.09.008},

issn = {1773-2247},

year  = {2017},

date = {2017-10-01},

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

volume = {41},

pages = {454-461},

abstract = {The prediction of the drug’s fate, once it is released from a pharmaceutical form, is one of the key topic in pharmaceutics and, to evaluate its release kinetics and effectiveness, the reproduction of the mixing conditions experienced by the pharmaceutical system is necessary. In this work a device reproducing the peristaltic waves of the stomach is presented, in order to obtain more reliable drug release profiles. Extended release commercial tablets of diclofenac were tested using both the conventional dissolution method and the new in vitro model proposed. The release profiles obtained using the conventional method and using the artificial stomach were found different both in shape and in magnitude. In particular, a drug concentration gradient along the stomach was realized, reflecting the poor mixing behavior in the model, similarly to what happen in the real physiology. Furthermore, also during the second stage of dissolution the evolutions were different, probably due to the higher shear experienced by the tablet during the first stage in the novel apparatus. The plasma concentration evolutions were predicted by a pharmacokinetic model starting from in vitro dissolution profiles. The comparison of the plasma concentrations confirmed that the dissolution kinetics strongly influences the drug evolution in the human body.},

keywords = {Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@article{Larsson2017,

title = {Effects of HPMC substituent pattern on water up-take, polymer and drug release: an experimental and modelling study},

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

url = {http://www.sciencedirect.com/science/article/pii/S0378517317305720},

doi = {10.1016/j.ijpharm.2017.06.064},

issn = {0378-5173},

year  = {2017},

date = {2017-08-07},

journal = {International Journal of Pharmaceutics},

volume = {528},

number = {1-2},

pages = {705-713},

abstract = {The purpose of this study was to investigate the hydration behavior of two matrix formulations containing the cellulose derivative hydroxypropyl methylcellulose (HPMC). The two HPMC batches investigated had different substitution pattern along the backbone; the first one is referred to as heterogeneous and the second as homogenous. The release of both the drug molecule theophylline and the polymer was determined. Additionally, the water concentrations at different positions in the swollen gel layers were determined by Magnetic Resonance Imaging. The experimental data was compared to predicted values obtained by the extension of a mechanistic Fickian based model. The hydration of tablets containing the more homogenous HPMC batch showed a gradual water concentration gradient in the gel layer and could be well predicted. The hydration process for the more heterogeneous batch showed a very abrupt step change in the water concentration in the gel layer and could not be well predicted. Based on the comparison between the experimental and predicted data this study suggests, for the first time, that formulations with HPMC of different heterogeneities form gels in different ways. The homogeneous HPMC batch exhibits a water sorption behavior ascribable to a Fick´s law for the diffusion process whereas the more heterogeneous HPMC batches does not. This conclusion is important in the future development of simulation models and in the understanding of drug release mechanism from hydrophilic matrices. },

keywords = {Erosion, HPMC, Hydrogel Characterization, Hydrogel Modeling, Mathematical modeling},

pubstate = {published},

tppubtype = {article}

}

@article{NPC02,

title = {Modeling of the behavior of natural polysaccharides hydrogels for bio-pharma applications},

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

url = {http://www.naturalproduct.us/index.asp

https://www.gruppotpp.it/wp-content/uploads/2017/06/Caccavo-et-al-NPC-126-867-871-2017-Abstract.pdf},

issn = {1934-578X},

year  = {2017},

date = {2017-07-31},

journal = {Natural Product Communications},

volume = {12},

number = {6},

pages = {867-871},

abstract = {Hydrogels, even if not exclusively obtained from natural sources, are widely used for pharmaceuticals and for biomedical applications. The reasons for their uses are their biocompatibility and the possibility to obtain systems and devices with different properties, due to variable characteristics of the materials. In order to effectively design and produce these systems and devices, two main ways are available: i) trial-and-error process, at least guided by experience, during which the composition of the system and the production steps are changed in order to get the desired behavior; ii) production process guided by the a-priori simulation of the systems’ behavior, thanks to proper tuned mathematical models of the reality. Of course the second approach, when applicable, allows tremendous savings in term of human and instrumental resources.

In this mini-review, several modeling approaches useful to describe the behavior of natural polysaccharide-based hydrogels in bio-pharma applications are reported. In particular, reported case histories are: i) the size calculation of micro-particles obtained by ultrasound assisted atomization; ii) the release kinetics from core-shell micro-particles, iii) the solidification behavior of blends of synthetic and natural polymers for gel paving of blood vessels, iv) the drug release from hydrogel-based tablets. This material can be seen as a guide toward the use of mathematical modeling in bio-pharma applications. 

},

keywords = {Hydrogel Characterization, Hydrogel Modeling, Hydrogels, Mathematical modeling, Modeling},

pubstate = {published},

tppubtype = {article}

}

@article{Simone}2017,

title = {Central Composite Design in HPMC granulation and correlations between product properties and process parameters},

author = {Veronica {De Simone} and Annalisa Dalmoro and Gaetano Lamberti and Matteo D'Amore and Anna Angela Barba},

url = {http://pubs.rsc.org/en/Content/ArticleLanding/2017/NJ/C7NJ01280B#!divAbstract},

doi = {10.1039/C7NJ01280B},

year  = {2017},

date = {2017-07-21},

journal = {New Journal of Chemistry},

volume = {41},

number = {14},

pages = {6504-6513},

abstract = {Particulate solids have a great interest in many industrial fields for both marketing reasons and technological aspects. In this study granular systems were achieved by wet granulation process using HydroxyPropyl MethylCellulose (HPMC) and distilled water as binder phase. Particulates with a defined size (450-2000 µm) and good flowability together with a high granulation process yield to reduce manufacturing scrap, were produced. To this aim a bench scale low-shear rate granulator apparatus was used; three process parameters were varied (impeller rotation speed, binder volume at constant mass, binder flow rate) and, for each parameter, three intensities have been used. HPMC granules production was planned by the Central Composite Design (CCD) statistical protocol, which has allowed to minimize the number of runs to perform for obtaining information about the relationship between granules properties and process parameters. The produced granules were stabilized by a dedicated dynamic drying apparatus, then separated by sieving and then characterized in terms of size and flowability properties. The results of the experimental campaign have been used to develop semi-empirical correlations between granulated products properties and process parameters. A second-order polynomial law has shown the best comparison between experimental data and model predicted values. These correlations can constitute a reliable tool to know more on the effect of operative parameters changes in HMPC or similar particulate solids production.},

keywords = {Granulation, HPMC},

pubstate = {published},

tppubtype = {article}

}

@article{Caccavo2017b,

title = {Mechanics and transport phenomena in agarose-based hydrogels studied by compression-relaxation tests},

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

url = {http://www.sciencedirect.com/science/article/pii/S0144861717302837},

doi = {10.1016/j.carbpol.2017.03.027},

year  = {2017},

date = {2017-07-01},

journal = {Carbohydrate Polymers},

volume = {167},

pages = {136\textendash144},

abstract = {Hydrogels are widespread materials, used in several frontier fields, due to their peculiar behavior: they couple solvent  mass transport to system mechanics, exhibiting viscoelastic and poroelastic characteristics. The full understanding of this behavior is crucial to correctly design such complex systems. In this study agarose gels has been investigated through experimental stress-relaxation tests and with the aid of a 3D poroviscoelastic model. At the investigated experimental conditions, the agarose gels samples show a prevalent viscoelastic behavior, revealing limited water transport and an increase of the stiffness as well as of the relaxation time along with the polymer concentration. The model parameters, derived from the fitting of some experimental data, have been generalized and used to purely predict the behavior of another set of gels. The stress-relaxation tests coupled with mathematical modeling demonstrated to be a powerful tool to study hydrogels’ behavior. },

keywords = {Hydrogel Characterization, Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@article{Caccavo2017,

title = {PoroViscoElastic model to describe hydrogels' behavior},

author = {Diego Caccavo and Gaetano Lamberti},

url = {http://www.sciencedirect.com/science/article/pii/S0928493116325760},

doi = {10.1016/j.msec.2017.02.155},

year  = {2017},

date = {2017-07-01},

journal = {Materials Science and Engineering: C},

volume = {76},

pages = {102\textendash113},

abstract = {Hydrogels are three-dimensional, cross-linked hydrophilic polymeric network able of absorb large amount of water. The mechanics of these systems is strictly coupled with the water transport resulting in the peculiar behavior known as poroviscoelasticy. This can be considered as sum of the viscoelastic behavior of the polymeric network and the poroelastic behavior caused by the water movement within the hydrogel. In this work a 3D monophasic model able to depict the poroviscoelastic behavior of these systems, within the field of nonlinear solid mechanics, is developed. The mass and momentum balances equations, supported by constitutive equations from non-equilibrium thermodynamics and by initial and boundary conditions, is implemented through the weak formulation in a commercial FEM-based software. A parametric study is performed in order to assess the relative importance of the model parameters on hydrogels' behavior.},

keywords = {Hydrogel Modeling},

pubstate = {published},

tppubtype = {article}

}

@article{Bochicchio2017,

title = {In vitro and ex vivo delivery of tailored siRNA-nanoliposomes for E2F1 silencing as a potential therapy for colorectal cancer},

author = {Sabrina Bochicchio and Barbara Dapas and Ilaria Russo and Carolina Ciacci and Ornella Piazza and Stefan {De Smedt} and Eline Pottie and Anna Angela Barba and Gabriele Grassi},

url = {http://www.sciencedirect.com/science/article/pii/S0378517317301011},

doi = {10.1016/j.ijpharm.2017.02.020},

year  = {2017},

date = {2017-06-20},

journal = {International Journal of Pharmaceutics},

volume = {525},

number = {2},

pages = {377\textendash387},

abstract = {Tailored developed nanoliposomes loaded with a siRNA against the transcription factor E2F1 (siE2F1), were produced and delivered to human colorectal adenocarcinoma cell lines and to intestinal human biopsies. siE2F1 loaded nanoliposomes were produced through a dedicated ultrasound assisted technique producing particles with about 40 nm size (Small Unilamellar Vesicles, SUVs) and 100% siRNA encapsulation efficiency. Compared to other production methods, the one proposed here can easily produce particles in the nanometric scale by suitable ultrasonic duty cycle treatments. Furthermore, SUVs have a high degree of size homogeneity, a relevant feature for uniform delivery behaviour.

siE2F1-loaded SUVs demonstrated a very low cytotoxicity in cells when compared to a commercial transfection agent. Moreover, SUVs loaded with siE2F1 were effective in the down regulation of the target in cultured colon carcinoma cells and in the consequent reduction of cell growth. Finally, a remarkable uptake and target silencing efficiencies were observed in cultured human biopsy of colonic mucosa. In conclusion, whereas further studies in more complex models are required, the siE2F1-SUVs generated have the potential to contribute to the development of novel effective inflammatory bowel diseases-associated colorectal cancer therapies for a future personalized medicine.},

keywords = {Micro and Nano Vectors},

pubstate = {published},

tppubtype = {article}

}

@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{Pavia}2017,

title = {Double Flow Bioreactor for In Vitro Test of Drug Delivery},

author = {Francesco {Carf\`{i} Pavia} and Vincenzo {La Carrubba} and Giulio Ghersi and Silvia Greco and Valerio Brucato},

url = {https://www.gruppotpp.it/wp-content/uploads/2017/03/09.-Carf\`{i}-Pavia-et-al-CDD-142-239-245-2017.pdf

http://benthamscience.com/journals/current-drug-delivery/volume/14/issue/2/page/239/},

doi = {10.2174/1567201813666160527141538},

year  = {2017},

date = {2017-02-08},

journal = {Current Drug Delivery},

volume = {14},

number = {2},

pages = {239-245},

abstract = {In this work, double-structured polymeric scaffolds were produced, and a double flow bioreactor was designed and set up in order to create a novel system to carry out advanced in vitro drug delivery tests. The scaffolds consists of a cylindrical porous matrix, are able to host cells, thus mimicking a three-dimensional tumor mass: moreover, a "pseudo-vascular" structure was embedded into the matrix, with the aim of allowing a flow circulation. The structure that emulates a blood vessel is a porous tubular-shaped scaffold prepared by Diffusion Induced Phase Separation (DIPS), with an internal lumen of 2 mm and a wall thickness of 200 micrometers. The as-prepared vessel was incorporated into a three-dimensional matrix, prepared by Thermally Induced Phase Separation (TIPS), characterized by a high porosity (about 95%) and pore size adequate to accommodate tumor cells and/or mesenchymal cells. The morphology of the multifunctional scaffolds is easy-tunable in terms of pore size, porosity and thickness and therefore adaptable to various cell or tissue types. At the same time, a double flow bioreactor was designed and built up, in order to be able to carry out biological tests on the scaffold under dynamic conditions. The device allows a separate control of the two flows (one for the tubular scaffold, one for the porous matrix) through the scaffolds. Preliminary characterizations and tests carried out suggest the presented system as a candidate to suitably "in vitro" assess the effects of different drugs on various cell populations.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gioia}2016,

title = {From genesis to revelation: the role of inflammatory mediators in chronic respiratory diseases and their control by nucleic acid-based drugs},

author = {Sante {Di Gioia} and Carla Sardo and Stefano Castellani and Barbara Porsio and Giuliana Belgiovine and Annalucia Carbone and Gaetano Giammona and Gennara Cavallaro and Massimo Conese},

url = {https://www.gruppotpp.it/wp-content/uploads/2017/03/11.-Di-Gioia-et-al-CDD-142-253-271-2017.pdf

http://benthamscience.com/journals/current-drug-delivery/volume/14/issue/2/page/253/},

doi = {10.2174/1567201813666160824142843},

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 = {253 - 271},

abstract = {Asthma, chronic obstructive pulmonary disease, cystic fibrosis, and idiopathic pulmonary fibrosis, are among the most common chronic diseases and their prevalence is increasing. Each of these diseases is characterized by the secretion of cytokines and pro-inflammatory molecules which are thought to play a critical role in their pathogenesis. Moreover, immune cells, particularly neutrophils, macrophages and dendritic cells as well structural cell such as epithelial and airway smooth muscle cells also are involved in the pathogenic cycle of these diseases. There is a pressing need for the development of new therapies for these pulmonary diseases, particularly as no existing treatment has been shown to reduce disease progression. HMGB1 (high-mobility group box 1), originally identified as a nuclear nonhistone protein with DNA-binding domains can be secreted by living and dying cells and it is now regarded as an important endogenous danger signaling molecule. Besides as a signal of tissue injury, HMGB1 is considered a powerful mediator of inflammation and high levels of HMGB1 are found in chronic lung diseases. However, the role of HMGB1 in respiratory diseases is still elusive but nevertheless these studies suggest an involvement of this cytokine in their pathogenesis. Nucleic acid-based drugs (NABDs) are a novel class of pharmaceuticals including antisense oligonucleotides, DNA-zymes, and RNA interference as mediated by small interfering RNA (siRNA), which are used to dampen the expression of disease-causing genes having therapeutic potential for controlling chronic airway diseases. Due to their inherent difficulties, such as for example sensitivity to endonucleases, their delivery in vivo should be assured by vectors. Non-viral lipid- and polymer-based nanosystems have acquired much importance in this context. In this review, we will discuss these emerging tools in gene therapy of chronic lung diseases, in particular the use of siRNA in the down-regulation of critical molecules in the pathogenesis of chronic lung diseases, with particular emphasis on HMGB1 as therapeutic target.},

keywords = {},

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{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{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{Piazza2016b,

title = {The effect of liver esterases and temperature on remifentanil degradation in vitro},

author = {Ornella Piazza and Sara Cascone and Linda Sessa and Edoardo {De Robertis} and Gaetano Lamberti},

url = {http://www.sciencedirect.com/science/article/pii/S0378517316305191},

doi = {10.1016/j.ijpharm.2016.06.043},

year  = {2016},

date = {2016-07-04},

journal = {International Journal of Pharmaceutics},

volume = {510},

number = {1},

pages = {359\textendash364},

abstract = {Remifentanil is a potent opioid metabolized by serum and tissue esterases; it is routinely administered to patients with liver failure as anaesthetic and analgo-sedative without variation in doses, even if prolonged clinical effects and respiratory depression have been observed in these patients.The aim of this study was to determine remifentanil enzymatic degradation kinetics bearing in mind the effect of liver esterases in order to trace a more accurate pharmacokinetic profile of the drug. Solution samples were taken over time and analysed to measure remifentanil concentration by HPLC. We reproduced the physiological settings, varying temperature and pH in vitro and evaluated the kinetics of degradation of remifentanil in the presence of Rhizopus Oryzae esterases, equine liver esterases and porcine liver esterases. Remifentanil kinetics of degradation was accelerated by porcine liver esterases. Remifentanil in vitro half-life decreases with increasing temperatures in the presence of porcine liver esterases. A drug model simulation considering the effect of temperature in the presence of liver esterases was developed.Remifentanil in vitro half-life decreases with increasing temperatures when porcine liver esterases are present. In this paper we propose a model for describing remifentanil degradation kinetics at various temperatures.},

keywords = {In vitro, Pharmacokinetics},

pubstate = {published},

tppubtype = {article}

}

@article{Coviello2016,

title = {Influence of borate amount on the swelling and rheological properties of the Scleroglucan/borax system},

author = {Tommasina Coviello and Silvia Margheritelli and Pietro Matricardi and Chiara {Di Meo} and Felice Cerreto and Franco Alhaique and Michela Abrami and Mario Grassi },

url = {http://onlinelibrary.wiley.com/doi/10.1002/app.42860/abstract},

doi = {10.1002/app.42860},

year  = {2016},

date = {2016-01-01},

journal = {Journal of Applied Polymer Science},

volume = {133},

number = {3},

pages = {42860 (1-10)},

abstract = {Scleroglucan is a fungal polysaccharide that, when dispersed in water, assumes a very stable triple helix structure. It has numerous industrial applications in different fields, such as food industry, cosmetics, and pharmaceutics. In the presence of borate ions, this polymer forms weak gels that, after freeze-drying and compaction, show an anisotropic swelling behavior, related to the borate/polymer ratio. By monitoring the evolution of the elastic and viscous moduli it was possible to follow the gel formation kinetics. The rheological properties of the network were studied as a function of crosslinking agent concentration and the corresponding flow curves and mechanical spectra were recorded. The kinetics of the crosslinking reaction was monitored by following the time evolution of the storage and loss moduli, after the addition of borate ions to the Scleroglucan system. Creep-recovery experiments allowed acquiring recoverable strain values and those of the critical stress above which a very high compliance of the sample is reached. Obtained results are to be related to the specific type of bonds between the polysaccharide chains and the crosslinking agent.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}