聚乙二醇-壳聚糖支链共聚物中脂质体的结构与稳定性

Bioorganicheskaia khimiia Pub Date : 2014-09-01
I M Deĭgen, E V Kudriashova
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引用次数: 0

摘要

由于脂质体具有生物相容性和低免疫原性,其作为一种药物传递系统在生物技术领域引起了极大的兴趣。但其稳定性低、易聚集等缺点仍然限制了其在医学上的应用。因此,如何在高分子材料的基础上获得有效的脂质体稳定剂是目前的实际问题。本文建议采用聚乙二醇改性壳聚糖(peg -壳聚糖)为基料的支链共聚物作为脂质体的稳定添加剂。建立了用mPEG-suc-NHS改性聚乙二醇分子共聚物合成壳聚糖的方法,得到了不同改性程度的聚乙二醇-壳聚糖共聚物,研究了聚乙二醇-壳聚糖络合物的形成对双棕榈酰磷脂酰胆碱(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。利用FTIR光谱和DLS方法发现,聚乙二醇-壳聚糖共聚物与脂质体中的阴离子基相互作用,形成具有静电性质的配合物。发现该共聚物与脂质体的主要结合位点是磷酸基和羰基。红外光谱分析表明,聚乙二醇-壳聚糖与脂质体形成复合物,使脂质体在储存过程中具有明显的抗聚集稳定性。考虑到聚集是限制脂质体在医学中使用的关键因素之一,这一结果尤其重要。这些结果为聚乙二醇-壳聚糖共聚物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输送系统。
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[Structure and stability of liposomes in complex with PEG-chitosan branched copolymer].

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.

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