两亲多糖纳米胶束作为药物缓释载体的制备及释药研究

Preparation and Drug Controlled-release of Biodegradable Amphiphilic Polysaccharide Nano-micelles as Drug Delivery Systems

【目的】合成葡聚糖接枝聚乳酸(DEX-g-PLA)两亲多糖共聚物,检测其纳米胶束的相关参数,初步探讨其纳米胶束在药物缓释方面的应用。【方法】采用偶联法合成DEX-g-PLA。用透射电子显微镜观察所形成胶束的形态;用动态光散射仪观察纳米胶束有效粒径的变化。体外药物释放实验考察其对不同水溶性药物的缓释作用。MTT法考察其生物相容性。【结果】DEX-g-PLA纳米胶束,呈球形,粒径在50～190nm之间,其有效粒径随聚乳酸含量的增加而增大。载药纳米胶束对疏水性维生素B2的缓释效果优于亲水性的5-氟尿嘧啶。MTT结果显示该纳米胶束具有良好的生物相容性。【结论】DEX-g-PLA纳米胶束具有良好的生物相容性,对疏水性药物的缓释作用优于亲水性药物,有望成为新型药物缓释载体。

[Objective] To investigate the preparation of polylactide-grafted dextran copolymer （DEX-g-PLA）, and to detect their correlative parameters and explore the application of nano-micelles for drug controlled-release. [Methods] The polylactide-grafted dextran eopolymer （DEX-g-PLA） was synthesized in a bulk lactide polymerization reaction using dextran derivative as macroinitiator and stannous octoate as catalyst. The surface morphology of the resulting nano-micelles was characterized by transmission electron microscopy and particle size was measured by dynamic light scattering. The controlled-release of drugs of different water-solubility was tested by in-vitro release studies, and the biocompatibility of nano-micelles was measured by MTT assay in vitro. [Results] The DEX-g-PLA nano-micelles were of round or elliptical shape and their average diameters ranged from 50 nm to 190 nm, which were increased with the increase of content of PLA in micelles. The in-vitro release studies indicated that the release of hydrophobic vitamin B2 from nano-micelles was obviously more sustained than that of hydrophilie 5-Fluorouracil. MTT assay suggested that DEX-g-PLA nano-micelles were of fine biocompatibility. [ Conclusion ] The release of hydrophobic drugs from the biocompatible micelles of DEX-g-PLA is obviously more sustained than that of hydrophilic drugs, suggesting it would be a promising carrier for drug delivery systems.