聚羟基丁酸酯缓释微粒作用下的埋植给药系统

Thermogelling implant drug delivery system with poly-3-hydroxybutyrate based on microparticles

制备了以壳聚糖水凝胶为基质的温度敏感型、可注射、并能够在体内生物降解的新型皮下埋植制剂,考察了该制剂中水溶性小分子药物的体外释放规律。为降低该类药物的释放速度,首先利用溶剂非溶剂法,以生物可降解的聚羟基丁酸酯为骨架,制备了抗癌药物5-氟尿嘧啶的微粒。在优化配比下,微粒收率达90%以上,包封率95%左右;然后将微粒温敏型水凝胶耦合制成复合给药系统。药物微粒化与温敏型水凝胶的耦合有效地控制了药物植入初期的“突释”问题,并将药物的释放周期延长至将近10个月。

A thermosensitive, injectable in situ gelling formulation was developed using naturally biodegradable chitosan hydrogel. The release profiles of a low water solubility drug, 5-fluorouracil （5-Fu）, an antineoplastic agent, using this formulation were then characterized. The rapid initial release of the drug was controlled by first microencapsulating the drug, and then mixing the microparticles with the thermosensitive gel. The microparticles were prepared by the solvent/non-solvent method, using biodegradable poly-3-hydroxybutyrate （PHB） as the scaffold to capsulate the 5-Fu. At an optimized drug to scaffold ratio, the recovery rate of the microparticles was over 90%, with an encapsulation efficiency of over 95%. The chitosan hydrogel containing these microparticles can accurately control the rapid initial release of the drug to give 10 months of sustained release.