聚电解质逐层组装的自膨胀微凝胶脉冲释放系统的研究

项目名称： 聚电解质逐层组装的自膨胀微凝胶脉冲释放系统的研究

项目编号： No.30801441

项目类型： 青年科学基金项目

立项/批准年度： 2009

项目学科： 化学工业

项目作者： 邹豪

作者单位： 中国人民解放军第二军医大学

项目金额： 19万元

中文摘要： 聚电解质逐层组装的自膨胀微凝胶是一种程序设定式的脉冲释药系统，它由高分子材料降解和膨胀压双重作用来精确时滞，并且释放响应快，能迅速达到有效浓度。它由可降解的高分子材料制成的微凝胶作为"核"，脂质或高分子作为"包衣"，随着微凝胶中高分子的不断降解，体系内部膨胀压不断增加，到达临界状态，"包衣"层被胀破，形成脉冲释药。本课题以壳聚糖作为核心材料，FITC-dextran为模型药物，PAH和PSS作为聚电解质包衣材料制备逐层组装的自膨胀微凝胶脉冲制剂。由于粒子的表面张力效应，根据拉普拉斯理论，较大粒子具有较小的表面张力，相比于小粒子更容易被内部核心的膨胀压胀破，导致时滞的差异。本题采用高压静电场成囊机制备微凝胶核心很好的解决了这一问题。实验第一部分建立了测定FITC-dextran含量的荧光分光光度计方法及考察不同条件下FITC-dextran的稳定性。实验第二部分为聚电解质逐层组装的壳聚糖自膨胀微凝胶的制备工艺及其性质考察。实验第三部分为载FITC-dextran聚电解质包衣微凝胶的处方设计。实验第四部分为聚电解质包衣微凝胶的体内释放过程和组织学研究。

中文关键词： 聚电解质;逐层组装;膨胀性;壳聚糖-海藻酸钠;FITC-dextran

英文摘要： This report aimed to introduce a novel "core-membrane" structural drug device suitable for spontaneous pulsed release without any external trigger. The core was prepared through gelatinization between calcium and alginate, treated with chitosan in media at the same time. The swelling pressure of the core, which governs the drug release, mainly comes from the degradation and pH-sensitive of the chitosan-alginate microgels. When the swelling pressure reaches to a critical value, the membrane outside can rupture, accompanyed drug massive release. The semipermeable membrane outside the microgel is made of polyelectrolytes including polycation poly (allylamine hydrochloride) (PAH) and polyanion sodium poly (styrene sulfonate) (PSS) sequentially depositing onto the core surface through electrostatic attraction. We investigated the size, surface charge, morphology and structure of the polyelectrolyte layer-by-layer coating of chitosan-alginate microgels (PCAM). Moreover, the permeability of membrane, the swelling capability of the core, the polymers used in PCAM were investigated to tailored the explosion time and subsequent release. At last, histological examination was carried and the release process of PCAM was observed in mice. There was no tissue damage or inflammatory reaction around the injection site. That demonstrated good biocompatibility and safety of PCAM. All the results suggest that the encapsulated substrate loaded in PCAM has a massive release after a lag phase and PCAM is a suitable and effective system for pulsed drug delivery.

英文关键词： Polyelectrolyte; Chitosan-Alginate; Microgels; Layer-by-layer; Pulsed drug delivery