@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{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{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{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}

}