ナノメディシンとナノテクノロジーのジャーナル

概要

Analysis of Operating Conditions Influencing the Morphology and In vitro Behaviour of Chitosan Coated Liposomes

Marco Venturini, Stefania Mazzitelli, Ivan Micetic, Camilla Benini, Jacopo Fabbri, Stefano Pozzi Mucelli, Federico Benetti and Claudio Nastruzzi

Among nanoparticle-based drug delivery formulations, lecithin/chitosan liposomes are promising candidates because of their biocompatibility, biodegradability and bioadhesion properties. Lecithin is a mixture of highly biocompatible phospholipids, while chitosan represents one of the most used polymers in pharmaceutical formulations. Their combination results in positively charged complexes that are able to sustain a specific, prolonged and controlled release. Scarce reproducibility and batch-to-batch variation in lecithin/chitosan liposome synthesis, as well as difficult scale-up to industrial production, is a major challenge for their utilization. Here we present a strictly controlled procedure, based on ethanol diffusion in water, which yields to a precise and reproducible self-organization of lecithin and chitosan molecules. We analysed the size, surface charge and stability of chitosan coated liposomes at different lecithin/chitosan ratios. We found that increasing the lecithin/chitosan ratio both mean particle size and surface charge were progressively reduced. A good stability was observed for all formulations, though interactions occurred in the presence of low amount of surface-adsorbed chitosan liposome vesicle. Chitosan coated liposomes interact with A549 and Caco-2 cells inducing low toxic effects only with prolonged incubation times. In conclusion, the proposed procedure provides good reproducibility in the formation of non-toxic and highly stable formulations of chitosan coated liposomes as drug delivery systems.