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[聚乙二醇-壳聚糖支链共聚物复合物中脂质体的结构与稳定性]

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

作者信息

Deĭgen I M, Kudriashova E V

出版信息

Bioorg Khim. 2014 Sep-Oct;40(5):595-607.

PMID:25895355
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.

摘要

由于其生物相容性和低免疫原性,脂质体作为一种药物递送系统在生物技术领域备受关注。然而,低稳定性和聚集倾向仍然限制了它们在医学上的应用。因此,实际问题是在聚合物材料基础上获得用于脂质体的有效稳定添加剂。在本文中,我们建议使用基于聚乙二醇修饰的壳聚糖(PEG-壳聚糖)的支化共聚物作为脂质体的稳定添加剂。开发了通过使用mPEG-suc-NHS用PEG分子修饰壳聚糖的共聚物合成方法,并获得了不同修饰度的PEG-壳聚糖共聚物,以研究PEG-壳聚糖的络合形成对二棕榈酰磷脂酰胆碱(DPPC)和心磷脂(CL)(80/20% w/w)混合阴离子脂质体结构和稳定性的影响。通过傅里叶变换红外光谱(FTIR)和动态光散射(DLS)方法发现,PEG-壳聚糖共聚物通过与脂质体中的阴离子基团相互作用形成静电性质的络合物。发现共聚物与脂质体的主要结合位点是磷酸基团和羰基。对红外光谱的分析表明,脂质体与PEG-壳聚糖的络合形成导致脂质体在储存时抗聚集的显著稳定。考虑到聚集是限制脂质体在医学上使用的关键因素之一,这一结果尤为重要。这些结果为共聚物PEG-壳聚糖作为稳定脂质体的有效添加剂提供了前景,并有望创造新的药物递送系统。

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