@article{Bochicchio2021,

title = {Polymer\textendashLipid Pharmaceutical Nanocarriers: Innovations by New Formulations and Production Technologies},

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

editor = {Thomas Rades},

url = {https://www.mdpi.com/1999-4923/13/2/198/htm},

doi = {10.3390/pharmaceutics13020198},

issn = {19994923},

year  = {2021},

date = {2021-02-02},

journal = {Pharmaceutics},

volume = {13(2)},

number = {198},

pages = {15},

abstract = {Some issues in pharmaceutical therapies such as instability, poor membrane permeability, and bioavailability of drugs can be solved by the design of suitable delivery systems based on the combination of two pillar classes of ingredients: polymers and lipids. At the same time, modern technologies are required to overcome production limitations (low productivity, high energy consumption, expensive setup, long process times) to pass at the industrial level. In this paper, a summary of applications of polymeric and lipid materials combined as nanostructures (hybrid nanocarriers) is reported. Then, recent techniques adopted in the production of hybrid nanoparticles are discussed, highlighting limitations still present that hold back the industrial implementation. },

keywords = {drug delivery, hybrid nanoparticles, lipids, nanotechnologies, polymers, production technologies},

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{Bochicchio2020b,

title = {Advances in Nanoliposomes Production for Ferrous Sulfate Delivery},

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

editor = {MDPI},

url = {https://www.mdpi.com/1999-4923/12/5/445/pdf},

doi = {10.3390/pharmaceutics12050445},

year  = {2020},

date = {2020-05-11},

journal = {Pharmaceutics},

volume = {12},

number = {5},

pages = {445},

abstract = {In this study, a continuous bench scale apparatus based on microfluidic fluid dynamic principles was used in the production of ferrous sulfate-nanoliposomes for pharmaceutical/nutraceutical applications, optimizing their formulation with respect to the products already present on the market. After an evaluation of its fluid dynamic nature, the simil-microfluidic (SMF) apparatus was first used to study the effects of the adopted process parameters on vesicles dimensional features by using ultrasonic energy to enhance liposomes homogenization. Subsequently, iron-nanoliposomes were produced at different weight ratios of ferrous sulfate to the total formulation components (0.06, 0.035, 0.02, and 0.01 w/w) achieving, by using the 0.01 w/w, vesicles of about 80 nm, with an encapsulation efficiency higher than 97%, an optimal short- and long-term stability, and an excellent bioavailability in Caco-2 cell line. Moreover, a comparison realized between the SMF method and two more conventional production techniques showed that by using the SMF setup the process time was drastically reduced, and the process yield increased, achieving a massive nanoliposomes production. Finally, duty-cycle sonication was detected to be a scalable technique for vesicles homogenization. },

keywords = {drug delivery, ferrous sulfate, nanoliposome, simil-microfluidic apparatus, sonication},

pubstate = {published},

tppubtype = {article}

}

@article{Bochicchio2020,

title = {Simil-Microfluidic Nanotechnology in Manufacturing of Liposomes as Hydrophobic Antioxidants Skin Release Systems},

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

url = {https://www.mdpi.com/2079-9284/7/2/22/pdf},

doi = {10.3390/cosmetics7020022},

year  = {2020},

date = {2020-04-03},

journal = {Cosmetics},

volume = {7},

number = {22},

pages = {13},

abstract = {Novel nanotechnologies represent the most attractive and innovative tools to date exploited by cosmetic companies to improve the effectiveness of their formulations. In this context, nanoliposomes have had a great impact in topical preparations and dermocosmetics, allowing the transcutaneous penetration and absorption of several active ingredients and improving the stability of sensitive molecules. Despite the recent boom of this class of delivery systems, their industrial production is still limited by the lack of easily scalable production techniques. In this work, nanoliposomes for the topical administration of vitamin D3, K2, E, and curcumin, molecules with high antioxidant and skin curative properties but unstable and poorly absorbable, were produced through a novel simil-microfluidic technique. The developed high-yield semi continuous method is proposed as an alternative to face the problems linked with low productive conventional methods in order to produce antioxidant formulations with improved features. The novel technique has allowed to obtain a massive production of stable antioxidant vesicles of an 84\textendash145 nm size range, negatively charged, and characterized by high loads and encapsulation efficiencies. The obtained products as well as the developed high-performance technology make the achieved formulations very interesting for potential topical applications in the cosmetics/cosmeceutical field. },

keywords = {antioxidants, cosmeceutics, nanoliposomes, simil-microfluidic technology, transdermal delivery},

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{Barba2019b,

title = {Coating of Nanolipid Structures by a Novel Simil-Microfluidic Technique: Experimental and Theoretical Approaches },

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

url = {https://www.mdpi.com/2079-6412/9/8/491/htm},

doi = {10.3390/coatings9080491},

year  = {2019},

date = {2019-08-02},

journal = {Coatings},

volume = {9},

number = {491},

pages = {1-15},

abstract = {Nanolipid vesicular structures are ideal candidates for the controlled release of various ingredients, from vitamins for nutraceutical purposes to chemoterapic drugs. To improve their stability, permeability, and some specific surface properties, such as mucoadhesiveness, these structures can require a process of surface engineering. The interaction of lipid vesicles with oppositely charged polyelectrolytes seems to be an interesting solution, especially when the negatively charged liposomes are complexed with the cationic chitosan. In this work, a novel simil-microfluidic technique was used to produce both chitosan-coated vesicles and a vegan alternative composed of cholesterol-free liposomes coated by Guar Hydroxypropyltrimonium Chloride (Guar-HC). The combination between the experimental approach, based on experimental observations in terms of Z-potential, and size evolutions, and the theoretical approach, based on concepts of saturation, was the methodology applied to define the best polycation concentration to fairly cover (vegan or not) liposomes without aggregation. The smart production of coated nanolipid structures was confirmed by characterizations of morphology, mucoadhesiveness, and stability.},

keywords = {Chitosan, Coated nanoliposomes, Guar guam, Liposome bioadhesive, Liposomi bioadesivi, Muchoadesiveness, Simil-microfluidic technique},

pubstate = {published},

tppubtype = {article}

}

@article{Barba2019,

title = {Lipid Delivery Systems for Nucleic-Acid-Based-Drugs: From Production to Clinical Applications},

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

url = {https://www.mdpi.com/1999-4923/11/8/360},

doi = {10.3390/pharmaceutics11080360},

year  = {2019},

date = {2019-07-24},

journal = {Pharmaceutics},

volume = {11},

number = {360},

abstract = {In the last years the rapid development of Nucleic Acid Based Drugs (NABDs) to be used in gene therapy has had a great impact in the medical field, holding enormous promise, becoming “the latest generation medicine” with the first ever siRNA-lipid based formulation approved by the United States Food and Drug Administration (FDA) for human use, and currently on the market under the trade name Onpattro™. The growth of such powerful biologic therapeutics has gone hand in hand with the progress in delivery systems technology, which is absolutely required to improve their safety and effectiveness. Lipid carrier systems, particularly liposomes, have been proven to be the most suitable vehicles meeting NABDs requirements in the medical healthcare framework, limiting their toxicity, and ensuring their delivery and expression into the target tissues. In this review, after a description of the several kinds of liposomes structures and formulations used for in vitro or in vivo NABDs delivery, the broad range of siRNA-liposomes production techniques are discussed in the light of the latest technological progresses. Then, the current status of siRNA-lipid delivery systems in clinical trials is addressed, offering an updated overview on the clinical goals and the next challenges of this new class of therapeutics which will soon replace traditional drugs},

keywords = {clinical trials, liposomes, Micro and Nano Vectors, NABDs, siRNA},

pubstate = {published},

tppubtype = {article}

}

@article{Dalmoro2019,

title = {Micronutrients encapsulation in enhanced nanoliposomal carriers by a novel preparative technology },

author = {Annalisa Dalmoro and Sabrina Bochicchio and Gaetano Lamberti and Paolo Bertoncin and Barbara Janssens and Anna Angela Barba},

url = {https://pubs.rsc.org/en/content/articlelanding/2019/ra/c9ra03022k},

doi = {10.1039/C9RA03022K},

year  = {2019},

date = {2019-06-25},

journal = {RSC Advances},

volume = {9},

pages = {19800-19812},

abstract = {Micronutrients administration by fortification of staple and complementary foods is a followed strategy to fight malnutrition and micronutrient deficiencies and related pathologies. There is a great industrial interest in preparation of formulations for joint administration of vitamin D3 and vitamin K2 for providing bone support, promoting heart health and helping boost immunity. To respond to this topic, in this work, uncoated nanoliposomes loaded with vitamin D3 and K2 were successfully prepared, by using a novel, high-yield and semi continuous technique based on simil-microfluidic principles. By the same technique, to promote and to enhance mucoadhesiveness and stability of the produced liposomal structures, chitosan was tested as covering material. By this way polymer\textendashlipid hybrid nanoparticles, encapsulating vitamin D3 and vitamin K2, with improved features in terms of stability, loading and mucoadhesiveness were produced for potential nutraceutical and pharmaceutical applications.},

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

pubstate = {published},

tppubtype = {article}

}

@article{Bochicchio2018,

title = {Design and production of hybrid nanoparticles with polymeric-lipid shell\textendashcore structures: conventional and next-generation approaches},

author = {Sabrina Bochicchio and Annalisa Dalmoro and Paolo Bertoncin and Gaetano Lamberti and Rouslan I. Moustafine and Anna Angela Barba },

url = {https://pubs.rsc.org/en/Content/ArticleLanding/2018/RA/C8RA07069E#!divAbstract},

doi = {10.1039/c8ra07069e},

year  = {2018},

date = {2018-09-27},

journal = {RSC Advances},

volume = {8},

pages = {34614\textendash34624},

abstract = {Liposomes constitute a class of prominent drug delivery systems due their cell-mimetic behaviour. Despite

their high biocompatibility, biodegradability and low intrinsic toxicity, their poor stability in biological fluids

as well as in stock conditions (high tendency to degrade or aggregate) have led to new approaches for

liposome stabilization (e.g., surface covering with polymers). Here, liposomes were enwrapped by the

natural biocompatible polymer chitosan to achieve stable shell\textendashcore nanostructures. Covered

nanoliposomes were produced using an innovative continuous method based on microfluidic principles.

The produced hybrid polymeric-lipid nanoparticles were characterized in terms of structural properties,

size and stability. Moreover, phenomenological aspects in formation of nanoliposomal vesicles and

chitosan layering, product quality (structure, size) and manufacturing yield related to this novel method

were compared with those of the conventional dropwise method and the obtained products. The

proposed simil-microfluidic method led to the production of stable and completely chitosan-covered

liposomes with a shell\textendashcore nanostructure that avoided the disadvantages inherent in the conventional

method (which are time-consuming and/or require bulky and more expensive equipment).},

keywords = {Micro and Nano Vectors},

pubstate = {published},

tppubtype = {article}

}

@article{Dalmoro2018b,

title = {Polymer-lipid hybrid nanoparticles as enhanced indomethacin delivery systems},

author = {Annalisa Dalmoro and Sabrina Bochicchio and Shamil F. Nasibullin and Paolo Bertoncin and Gaetano Lamberti and Anna Angela Barba and Rouslan I. Moustafine},

url = {https://www.sciencedirect.com/science/article/pii/S0928098718302331},

doi = {10.1016/j.ejps.2018.05.014},

year  = {2018},

date = {2018-08-30},

journal = {European Journal of Pharmaceutical Sciences},

volume = {121},

pages = {16-28},

abstract = {Non-steroidal anti-inflammatory drugs (NSAIDs), i.e. indomethacin used for rheumatoid arthritis and non-rheumatoid inflammatory diseases, are known for their injurious actions on the gastrointestinal (GI) tract. Mucosal damage can be avoided by using nanoscale systems composed by a combination of liposomes and biodegradable natural polymer, i.e. chitosan, for enhancing drug activity.



Aim of this study was to prepare chitosan-lipid hybrid delivery systems for indomethacin dosage through a novel continuous method based on microfluidic principles. The drop-wise conventional method was also applied in order to investigate the effect of the two polymeric coverage processes on the nanostructures features and their interactions with indomethacin. Thermal-physical properties, mucoadhesiveness, drug entrapment efficiency, in vitro release behavior in simulated GI fluids and stability in stocking conditions were assayed and compared, respectively, for the uncoated and chitosan-coated nanoliposomes prepared by the two introduced methods.



The prepared chitosan-lipid hybrid structures, with nanometric size, have shown high indomethacin loading (about 10%) and drug encapsulation efficiency up to 99%. TEM investigation has highlighted that the developed novel simil-microfluidic method is able to put a polymeric layer, surrounding indomethacin loaded nanoliposomes, thicker and smoother than that achievable by the drop-wise method, improving their storage stability. Finally, double pH tests have confirmed that the chitosan-lipid hybrid nanostructures have a gastro retentive behavior in simulated gastric and intestinal fluids thus can be used as delivery systems for the oral-controlled release of indomethacin.



Based on the present results, the simil-microfluidic method, working with large volumes, in a rapid manner, without the use of drastic conditions and with a precise control over the covering process, seems to be the most promising method for the production of suitable indomethacin delivery system, with a great potential in industrial manufacturing.},

keywords = {Micro and Nano Vectors},

pubstate = {published},

tppubtype = {article}

}

@article{Bochicchio2017b,

title = {On the design of tailored liposomes for KRX29 peptide delivery },

author = {Sabrina Bochicchio and Marina Sala and Antonia Spensiero and Maria Carmina Scala and Isabel Gomez-Monterrey and Gaetano Lamberti and Anna Angela Barba },

url = {http://pubs.rsc.org/en/Content/ArticleLanding/2017/NJ/C7NJ03115G},

doi = { 10.1039/C7NJ03115G},

issn = {1144-0546},

year  = {2017},

date = {2017-12-01},

journal = {New Journal of Chemistry},

volume = {41},

number = {19},

pages = {11280-11290},

abstract = {The high interest in therapeutic peptides, due to the specificity of their mechanisms of action, has stimulated the research of new delivery strategies to overcome bioavailability problems concerning the use of peptides in their naked form. In particular, in this study, a novel small cyclic peptide, the KRX29, with a potential therapeutic effect on Heart Failure (HF) pathology, was encapsulated into large and unilamellar small vesicles (LVs, SUVs) by the thin film-hydration method followed by ultrasound assisted size reduction processes, generating loaded liposomes with nanometric sizes. Loaded and unloaded liposomes were produced exploring three different formulations by changing the charge ratio (-/+) between the anionic phosphatidylglycerol (PG) and the cationic KRX29 peptide. LVs and SUVs were designed using a 1:1, 7:1 and 13:1 (-/+) PG/KRX29 charge ratio and, for each formulation, the charge effect on liposomes morphology, size and zeta potential were analyzed together with peptide encapsulation performance, load, recovery efficiencies and stability through an analytical HPLC protocol purposely developed. Best results in terms of encapsulation in nanoliposomal formulation for KRX29 delivery, were achieved using a 13:1 (-/+) charge ratio (99 % in 35 nm SUVs). The influence of PG/KRX29 charge ratio on the recovery efficiencies was also investigated obtaining that the maximal peptide recovery from liposomes (81 \textendash 94 %) was achieved by using a 1:1 (-/+) charge ratio formulation and pure ethanol as solvent for the extraction.},

keywords = {liposome, peptide},

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{Piazza2016,

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

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

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

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

doi = {10.2174/1567201813666160512150710},

year  = {2017},

date = {2017-02-08},

issuetitle = {NEW TRENDS IN GENE THERAPY: MULTIDISCIPLINARY APPROACHES TO SIRNAS CONTROLLED DELIVERY},

journal = {Current Drug Delivery},

volume = {14},

number = {2},

pages = {246 - 252},

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

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

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

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

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

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

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{D'Apolito2016,

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

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

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

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

doi = {10.2174/1567201813666160813172047},

year  = {2017},

date = {2017-02-08},

issuetitle = {NEW TRENDS IN GENE THERAPY: MULTIDISCIPLINARY APPROACHES TO SIRNAS CONTROLLED DELIVERY},

journal = {Current Drug Delivery},

volume = {14},

number = {2},

pages = {231 - 238},

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

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

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bochicchio2016b,

title = {New preparative approaches for micro and nano drug delivery carriers},

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

url = {https://www.gruppotpp.it/wp-content/uploads/2017/03/05.-Bochicchio-et-al-CDD-142-203-215-2017.pdf

http://benthamscience.com/journals/current-drug-delivery/volume/14/issue/2/page/203/},

doi = {10.2174/1567201813666160628093724},

year  = {2017},

date = {2017-02-08},

issuetitle = {NEW TRENDS IN GENE THERAPY: MULTIDISCIPLINARY APPROACHES TO SIRNAS CONTROLLED DELIVERY},

journal = {Current Drug Delivery},

volume = {14},

number = {2},

pages = {203 - 215},

abstract = {The full success of pharmacological therapies is strongly depending from the use of suitable, efficient and smart drug delivery systems (DDSs). Thus DDSs development is one of the main challenges in pharmaceutical industry both to achieve tailored carrier systems based on drug features and to promote manufacturing innovations to reduce energetic resources, emissions, wastes and risks. Main functions of an ideal DDS are: to protect loaded active molecules from degradation in physiological environments; to deliver them in a controlled manner and towards a specific organ or tissue, to allow the maintenance of the drug level in the body within therapeutic window. Smart features, such as those able to induce active molecule release upon the occurrence of specific physiological stimuli, are also desirable. Under the manufacturing point of view, the current industrial scenery is obliged to respond to the increasing market requirements and to the mandatory rules in sustainable productions such as raw material and energy savings.

In this work a general framework on drug delivery systems preparation techniques is presented. In particular two sections on innovation in preparative approaches carried out are detailed. These latter involve the use of microwave and ultrasonic energy applied in the production of polymeric and lipidic delivery systems on micro- and nanometric scale. The novelties of these preparative approaches are emphasized and examples of developed drug delivery carriers, loaded with vitamins and drug mimicking siRNA, are shown.},

keywords = {Micro and Nano Vectors},

pubstate = {published},

tppubtype = {article}

}

@article{Dalmoro2016b,

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

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

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



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



},

doi = {10.2174/1567201813666160721142202},

year  = {2017},

date = {2017-02-08},

issuetitle = {NEW TRENDS IN GENE THERAPY: MULTIDISCIPLINARY APPROACHES TO SIRNAS CONTROLLED DELIVERY},

journal = {Current Drug Delivery},

volume = {14},

number = {2},

pages = {216 - 223},

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

keywords = {Hydrogel Characterization},

pubstate = {published},

tppubtype = {article}

}

@article{Bochicchio2016,

title = {Vitamin delivery: Carriers based on nanoliposomes produced via ultrasonic irradiation},

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

url = {http://www.sciencedirect.com/science/article/pii/S0023643816300251},

doi = {10.1016/j.lwt.2016.01.025},

year  = {2016},

date = {2016-06-01},

journal = {LWT - Food Science and Technology},

volume = {69},

pages = {9-16},

abstract = {In recent years much attention has been focused on using lipid carriers as potential delivery systems for bioactive molecules due to their favorable properties such as high biocompatibility, size and composition versatility. In this paper formulation, preparation and characterization of liposomes, a class of powerfully versatile lipidic carriers, produced by means of an innovative ultrasound-assisted approach based on the thin-film hydration method, are presented and discussed. The main aim of this study is to obtain nanostructures (Small Unilamellar Vesicles, SUVs), less than 100 nm in size, loaded with different vitamins (B12, tocopherol and ergocalciferol), starting from lipidic microstructures (Multilamellar Large Vesicles, MLVs). Suitable formulations, sonication protocols and nanoliposomes were pointed out. SUVs with diameter size ranging from 40 nm to 51 nm were achieved starting from MLVs with a diameter range of 2.9 - 5.7 μm. Starting from MLVs with higher encapsulation efficiency for all kind of vitamins, SUVs with an encapsulation efficiency of 56% for vitamin B12, 76% for α-tocopherol and 57% for ergocalciferol were obtained. Stability tests have shown that the used lipid composition allows to keep intact the nanovesicles and their content for more than 10 days if incubated at simulated extracellular environment conditions.},

keywords = {Micro and Nano Vectors},

pubstate = {published},

tppubtype = {article}

}

@article{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{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}

}