[Structure and stability of liposomes in complex with PEG-chitosan branched copolymer].

Abstract

Liposomes are of great interest in biotechnology, as a drug delivery systems, due to their biocompatibility and low immunogenicity. However, low stability and tendency to aggregate still limits their application in medicine. Therefore, the actual problem is to obtain the effective stabilizing additives for the liposomes on the base of polymeric materials. In this paper we suggested to use the branched copolymers on the base of chitosan modified by polyethylene glycol (PEG-chitosan) as stabilizing additives for the liposomes. The method of copolymer synthesis of chitosan modified with PEG molecules by using mPEG-suc-NHS was developed and the PEG-chitosan copolymers of different modification degrees were obtained to investigate the influence of the complex formation of PEG-chitosan on the structure and stability of mixed anionic liposomes of dipalmitoylphosphatidylcholine (DPPC) and cardiolipin (CL) (80/20% w/w). It has been found by using FTIR spectroscopy and DLS methods that the PEG-chitosan co-polymers form a Complex of electrostatic nature by interaction with the anionic groups in liposomes. It was found that the main binding sites of the copolymer with liposomes are phosphate and carbonyl groups. Analysis of the IR spectra yields that the complex formation of liposomes with PEG-chitosan resulted to significant stabilization of liposomes against aggregation upon storage. This result is particularly important, taking into account the fact that the aggregation is one of the key factors limiting the use of liposomes in medicine. These results offer the prospect of the copolymer PEG-chitosan as an effective additive for stabilizing liposomes and hold promise for creating new drug delivery systems.