Abstract

Application of branched copolymers of polyethylene glycol and chitosan (PEG-chitosan) as stabilizing agents for anionic liposomes was shown to improve considerably liposomes storage stability. In the course of the work, an efficient and convenient approach to synthesis of PEG-chitosan copolymers through chemical modification of chitosan amino groups with monomethoxy-PEG-N-hydroxysuccinimidyl succinate (mPEG-suc-NHS) was developed. Chitosan with varying degree of PEGylation were obtained and used as stabilizing agents for anionic liposomes prepared of dipalmitoylphosphatidylcholine-cardiolipin, 80/20 by weight. The molecular mechanism of complex formation between the anionic liposomes and PEG-chitosan was studied by methods of FTIR spectroscopy and dynamic light scattering. Phosphate and carbonyl groups were found to be the main sites of the aminopolysaccharide binding. Stabilization of the complexes is mainly achieved through electrostatic interactions between anionic groups of cardiolipin and free amino groups of PEG-chitosan. The method of liposome stabilization is promising for the development of new drug delivery systems.

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