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背景:环糊精高分子和聚乙烯醇均具有无毒性及良好的生物相容性和力学性能,已被广泛用于生物医用材料,是近代生物制药及剂型研究的重要功能材料之一。目的:观察环糊精以共价键键合到聚乙烯醇后的药物控制释放性能,并探讨其药控释放机制。设计、时间及地点:观察性实验,于2008年在西北工业大学理学院应用化学系实验室和咸阳师范学院化学与化工学院实验室完成。材料:聚乙烯醇为天津天大实验化工厂产品,β-环糊精为上海三浦化工有限公司产品,喜树碱由西安近代化学研究所提供。方法:分别合成单6-对甲基苯磺酰β-环糊精酯和单6-甲酰基β-环糊精,利用缩醛化反应将醛基化β-环糊精固载到聚乙烯醇大分子链上,合成出聚乙烯醇固载β-环糊精的线性环糊精高分子。观察聚乙烯醇固载β-环糊精与模型药物喜树碱的包合作用;紫外可见分光光度仪测定不同环糊精固载量的聚乙烯醇-β-环糊精膜在不同pH值下释放药物的含量。主要观察指标:聚乙烯醇固载β-环糊精的合成条件及药物累计释放率。结果:合成聚乙烯醇固载β-环糊精高分子的最佳反应条件是反应时间2h,温度70℃,单6-甲酰基β-环糊精与聚乙烯醇的质量比小于等于4∶1。药物释放实验结果表明,聚乙烯醇固载β-环糊精因包合增溶作用促进了水难溶性药物的释放。在pH=11时,喜树碱的累积释放量和释放速率随着β-环糊精含量的变化不明显,而在pH=2的介质中,随着β-环糊精含量的增加,喜树碱的累积释放量和释放速率有了明显的增加。结论:对于致密的聚乙烯醇膜,β-环糊精的键入可能起到了致孔作用,增加了水分子的渗透能力和药物的扩散能力,有助于药物释放,但对于难溶药物,环糊精的增溶性能在药物的促释过程中起重要的作用。
BACKGROUND: Cyclodextrin polymers and polyvinyl alcohol are nontoxic and have good biocompatibility and mechanical properties. They have been widely used in biomedical materials and are one of the most important functional materials in modern biopharmaceutical and formulation research. OBJECTIVE: To observe the controlled release of cyclodextrin covalently bonded to polyvinyl alcohol and to explore its drug release mechanism. DESIGN, TIME AND SETTING: The observational experiment was completed in 2008 by Laboratory of Applied Chemistry and Faculty of Chemistry and Chemical Engineering, Xi’nan Normal University. Materials: Polyvinyl alcohol is a product of Tianjin Tianda Experimental Chemical Factory, β-cyclodextrin is a product of Shanghai Miura Chemical Co., Ltd., and camptothecin is provided by Xi’an Modern Chemistry Research Institute. Methods: β-Cyclodextrin mono-6-p-methylbenzenesulfonyl and β-Cyclodextrin were synthesized respectively. The aldehyde β-cyclodextrin was immobilized on polyethylene Alcohol macromolecular chains, synthesis of polyvinyl alcohol-loaded β-cyclodextrin linear cyclodextrin polymer. Β-cyclodextrin immobilized on polyvinyl alcohol and the model drug camptothecin were observed. UV-vis spectrophotometry was used to determine the effect of polyvinyl alcohol-β-cyclodextrin films with different cyclodextrins loadings on different pH values Drug release under the content. MAIN OUTCOME MEASURES: Synthesis conditions and drug cumulative release rate of β-cyclodextrin immobilized on polyvinyl alcohol. Results: The optimum reaction conditions for synthesizing β-cyclodextrin polymer were as follows: the reaction time was 2h, the temperature was 70 ℃, the mass ratio of mono-6-formyl β-cyclodextrin to polyvinyl alcohol was less than or equal to 4: 1. The results of drug release experiment showed that inclusion and solubilization of β-cyclodextrin immobilized on polyvinyl alcohol promoted the release of water-insoluble drugs. At pH = 11, the cumulative release and the release rate of camptothecin did not change significantly with the content of β-cyclodextrin, but in the medium with pH = 2, with the increase of β-cyclodextrin content, The cumulative release and release rate of the alkali had a significant increase. CONCLUSIONS: For dense polyvinyl alcohol film, β-cyclodextrin may play a key role in the pore-forming process, increasing the penetration of water molecules and the drug’s ability to diffuse, which helps to release the drug. However, for insoluble drugs, The solubilization of dextrin plays an important role in the process of drug release.