Liposomes for siRNA and small molecule delivery

SCHLICH, MICHELE

2017-04-11

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Abstract

In the last decades, liposomes have been extensively investigated as carriers for the delivery of a wide range of pharmaceutically active compounds and macromolecules, with the aim of modifying and improving their biopharmaceutical properties. In this work, the design and development of nano structured liposomal vehicles for the delivery of short interfering RNAs (siRNAs) and antiinflammatory agents is presented. Specifically, in the first section, different types of liposomes, including the appropriate surface modification with peptidic or small molecules targeting agents, have been designed and used to protect and deliver short interfering RNAs to neuronal primary and brain tumor cells. For both the formulations the physico-chemical properties, entrapment efficiency, stability, cell uptake and toxicity were evaluated. In one case, the knockdown efficiency of siRNA against alpha synuclein was evaluated and proposed as a possible treatment for Parkinson's disease. The second section presents the first report (to the best of our knowledge) of a combined use of a commercial needle-free jet injector with a liposomal formulation. In this work, the feasibility of the administration of liposomal suspension through the cited medical device was assessed by monitoring the physico-chemical properties of the vesicles before and after the administration through the skin ex-vivo. The positive results reported include the needle-free injector among the possible administration methods for liposomes, thus broadening the applications of such delivery systems.