聚乙烯醇固载β-环糊精线性高聚物的合成及其药物控制释放

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β-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人分了链上,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2 h,温度70℃,单β-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件药物的释放.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约物的促释过程中起重要的作用.

Polyvinyl alcohol containing beta-cyclodextrin linear high polymer Synthesis and drug controlled-release

BACKGROUND: Both cyclodextrin high polymer and polyvinyl alcohol (PVA) have been widely applied as biomedical materials owing to their characteristics including no toxicity and good biocompatibility and mechanical property and have become important functional materials of biological drug manufacture and medication research.OBJECTIVE: To observe the drug controlled release property of β-cyclodextrin (β-CD) loaded onto PVA by the covalent bond and to investigate the possible mechanisms of action. DESIGN, TIME AND SETTING: An observational experiment was performed at the Laboratories of Applied Chemistry, College of Science, Northwestern Polytechnical University, and College of Chemistry & Chemical Engineering, Xiangyang Normal University in 2008. MATERIALS: PVA (Tianda Experimental and Chemical Plant, Tianjin, China), β-CD (Sanpu Chemical Engineering Co.,Ltd., Shanghai, China) and camptothecin (Modern Times Chemical Institute, Xi'an, China) were used in this study. METHODS: Mono-6-O-tosyl-β-CD and mono-6-formyl-β-CD were synthesized separately. Silylatedβ-CD was loaded onto polymer chain of PVA by acetalization to produce PVA containingβ-CD (PVA-β-CD) linear high polymer. The clathration between PVA-β-CD and camptothecin was observed. Drug-release content of PVA-β-CD membranes under different pH values was determined through the use of ultraviolet-visible spectrophotometer. MAIN OUTCOME MEASURES: Synthesis condition and drug release rate of PVA-β-CD. RESULTS: The best condition for synthesis of PVA-β-CD linear high polymer comprised reaction time 2 hours, temperature 70 ℃, and the mass ratio of mono-6-formyl-β-cyclodextrin to PVA not higher than 4:1. Experimental results regarding drug release revealed that PVA-β-CD promoted water-insoluble drug release owing to its clathration and solubilization. Withβ-CD content increasing, camptothecin release amount and release velocity had no significant change in pH 11 medium but increased greatly in pH 2 medium. CONCLUSION: As for compact PVA membrane, addition ofβ-CD possibly leads to pore formation, thus promoting water molecule infiltration and drug diffusion, beneficial to drug release, and simultaneously, the solubilization of β-CD plays an important role in promoting the release of insoluble drug.