PRIN 2010-11

@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{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{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{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{Dalmoro2014,

title = {Single-Pot Semicontinuous Bench Scale Apparatus To Produce Microparticles},

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

url = {http://pubs.acs.org/doi/abs/10.1021/ie403308q},

doi = {10.1021/ie403308q},

issn = {0888-5885},

year  = {2014},

date = {2014-02-01},

journal = {Industrial \& Engineering Chemistry Research},

volume = {53},

number = {7},

pages = {2771--2780},

publisher = {ACS Publications},

abstract = {This work presents both the design of a novel process to produce microparticles with a shell−core structure and a bench scale apparatus purposely realized. The developed process was designed to respond to mandatory needs of process intensification. It involved the coupling of two emergent technologies: atomization assisted by ultrasonic energy and microwave heating. The former was used to atomize polymeric solutions; the latter was applied to stabilize the produced droplets by drying. Both operations were performed in the same vessel with the aim to have a single-pot process chamber and were carried out by a semicontinuous procedure. Basic design criteria and advantages of the ultrasonic−microwave coupled operations in the realized apparatus are presented and discussed. Results of testing and of operating runs to produce shell−core microparticles are also reported, emphasizing the main features of the produced particles.},

keywords = {Micro and Nano Vectors},

pubstate = {published},

tppubtype = {article}

}

@article{Bochicchio2014,

title = {Liposomes as siRNA Delivery Vectors},

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

url = {http://www.eurekaselect.com/128256/article},

doi = {10.2174/1389200216666150206124913},

issn = {1389-2002},

year  = {2014},

date = {2014-01-01},

journal = {Current drug metabolism},

volume = {15},

number = {9},

pages = {882--892},

publisher = {Bentham Science Publishers},

abstract = {Nucleic Acid Based Drugs (NABDs) constitute a class of promising and powerful therapeutic new agents with limited side effects, potentially useable against a wide range of diseases, including cancer. Among them, the short interfering RNAs (siRNAs), represent very effective molecules. Despite their in vitro efficacy, the major drawback that limits siRNAs usage consists in a difficult delivery due to their very low stability in physiological fluids, and to their limited membrane-permeability through physiological barriers. On the other hand, the liposomes (lipid bilayers closed in vesicles of various sizes) represent interesting drug delivery systems (DDSs) which can be tailored in order to get the best performance in terms of load, vesicle size and transfection yield. In this work, the current state of study in these two fields, and the connections between them, are briefly summarized.},

keywords = {Drug Delivery Systems, liposome, Micro and Nano Vectors, siRNA},

pubstate = {published},

tppubtype = {article}

}

@article{Barba2014c,

title = {Biocompatible nano-micro-particles by solvent evaporation from multiple emulsions technique},

author = { Anna Angela Barba and Annalisa Dalmoro and Matteo D'Amore and Clara Vascello and Gaetano Lamberti},

url = {http://link.springer.com/10.1007/s10853-014-8224-1},

doi = {10.1007/s10853-014-8224-1},

issn = {0022-2461},

year  = {2014},

date = {2014-01-01},

journal = {Journal of Materials Science},

volume = {49},

number = {14},

pages = {5160--5170},

publisher = {Springer US},

abstract = {In this study, a method based on a multiple emulsions system was developed for the production of polymeric nano and micro-vectors. The possibility to apply an unified preparation technique to different polymers, such as polyesters [polycaprolactone, poly-dl-lactide, poly(dl-lactide-co-caprolactone) = 70/30] and polyacrylates [poly(methylmethacrylate\textendashacrylic acid) = 73/27], loaded with different model molecules (budesonide, tamoxifen, and $alpha$-tocopherol) was explored. After selecting the best operating conditions, especially for emulsification and separation, the technique proved to be readily adaptable for production of both nano and micro-particles with different morphologies, depending on type of polymer, and consequently on solvent used for solubilization: nano-particles, with a round shape and a smooth surface, for polyesters, otherwise micro-particles for the polyacrylate polymer, owing to the presence of hydrophilic co-solvents, that caused both an easy coalescence between the oil and water phases, thus enlarged particles size, and a high porosity. Even the yield of encapsulation was influenced by the presence of hydrophilic co-solvents, causing a higher yield for nano-vectors. Polyesters-based nano-vectors showed release times of molecules, linked to their degradation time, higher than 8 months that make them useful to formulate injectable or implantable drug delivery systems. Polyacrylate-based micro-vectors showed an enteric behavior, interesting for designing solid pharmaceutical formulations for oral delivery. Therefore, the technique demonstrated to assure a broad application in drug delivery research.},

keywords = {Micro and Nano Vectors},

pubstate = {published},

tppubtype = {article}

}

@article{Barba2014a,

title = {Ultrasonic energy in liposome production: process modelling and size calculation},

author = { Anna Angela Barba and Sabrina Bochicchio and Gaetano Lamberti and Annalisa Dalmoro},

url = {http://xlink.rsc.org/?DOI=c3sm52879k},

doi = {10.1039/c3sm52879k},

issn = {1744-683X},

year  = {2014},

date = {2014-01-01},

journal = {Soft Matter},

volume = {10},

number = {15},

pages = {2574},

publisher = {The Royal Society of Chemistry},

abstract = {The use of liposomes in several fields of biotechnology, as well as in pharmaceutical and food sciences is continuously increasing. Liposomes can be used as carriers for drugs and other active molecules. Among other characteristics, one of the main features relevant to their target applications is the liposome size. The size of liposomes, which is determined during the production process, decreases due to the addition of energy. The energy is used to break the lipid bilayer into smaller pieces, then these pieces close themselves in spherical structures. In this work, the mechanisms of rupture of the lipid bilayer and the formation of spheres were modelled, accounting for how the energy, supplied by ultrasonic radiation, is stored within the layers, as the elastic energy due to the curvature and as the tension energy due to the edge, and to account for the kinetics of the bending phenomenon. An algorithm to solve the model equations was designed and the relative calculation code was written. A dedicated preparation protocol, which involves active periods during which the energy is supplied and passive periods during which the energy supply is set to zero, was defined and applied. The model predictions compare well with the experimental results, by using the energy supply rate and the time constant as fitting parameters. Working with liposomes of different sizes as the starting point of the experiments, the key parameter is the ratio between the energy supply rate and the initial surface area.},

keywords = {Micro and Nano Vectors},

pubstate = {published},

tppubtype = {article}

}

@article{author,

title = {Analysis of Size Correlations for Microdroplets Produced by Ultrasonic Atomization},

author = { Annalisa Dalmoro and Anna Angela Barba and Matteo D'Amore},

url = {http://www.hindawi.com/journals/tswj/2013/482910/},

doi = {10.1155/2013/482910},

issn = {1537-744X},

year  = {2013},

date = {2013-01-01},

journal = {The Scientific World Journal},

volume = {2013},

pages = {1--7},

abstract = {Microencapsulation techniques are widely applied in the field of pharmaceutical production to control drugs release in time and in physiological environments. Ultrasonic-assisted atomization is a new technique to produce microencapsulated systems by a mechanical approach. Interest in this technique is due to the advantages evidenceable (low level of mechanical stress in materials, reduced energy request, reduced apparatuses size) when comparing it to more conventional techniques. In this paper, the groundwork of atomization is introduced, the role of relevant parameters in ultrasonic atomization mechanism is discussed, and correlations to predict droplets size starting from process parameters and material properties are presented and tested.},

keywords = {Micro and Nano Vectors},

pubstate = {published},

tppubtype = {article}

}

@article{Dalmoro2013,

title = {Droplet size prediction in the production of drug delivery microsystems by ultrasonic atomization.},

author = { Annalisa Dalmoro and Matteo D'Amore and Anna Angela Barba},

url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=3829785\&tool=pmcentrez\&rendertype=abstract},

issn = {2239-9747},

year  = {2013},

date = {2013-01-01},

journal = {Translational medicine @ UniSa},

volume = {7},

number = {2},

pages = {6--11},

publisher = {Universit},

abstract = {Microencapsulation processes of drugs or other functional molecules are of great interest in pharmaceutical production fields. Ultrasonic assisted atomization is a new technique to produce microencapsulated systems by mechanical approach. It seems to offer several advantages (low level of mechanical stress in materials, reduced energy request, reduced apparatuses size) with respect to more conventional techniques. In this paper the groundwork of atomization is briefly introduced and correlations to predict droplet size starting from process parameters and material properties are presented.},

keywords = {dimensionless, Micro and Nano Vectors, microparticles size prediction, numbers in atomization, ultrasonic atomization},

pubstate = {published},

tppubtype = {article}

}