罗替戈汀微球的制备及体内药动学考察

Preparation of rotigotine-loaded microspheres and its pharmacokinetics in rats

目的:制备可实现持续多巴胺能刺激治疗帕金森病的罗替戈汀缓释微球,并进行体内外评价。方法:采用O/W乳化溶剂挥发法制备微球,并对其包封率、粒径、体外释放、体内药动学等进行了考察。结果:不同高分子及组合制备的罗替戈汀微球释药特性有明显差别,采用最优处方制备的罗替戈汀微球载药量为27.0%,包封率为90.2%,平均粒径为71.5μm,扫描电镜观察结果显示,微球表面光滑圆整,体外可持续缓慢释放14 d,体内药动学结果表明,罗替戈汀微球具有明显的缓释特征,血浆浓度在给药后96 h达峰,C max为(6.27±1.32)ng·mL-1,可以检测到给药后14 d。结论:所制备的罗替戈汀微球体内可持续缓慢释药达2周,达到了预期目的。

Abstract：Objective： To prepare rotigotine-loaded microspheres （RoMS） to achieve continuous dopaminergic stimulation （CDS） for the treatment of Parkinson＇s disease （PD）. Methods： Rotigotine was encapsulated into biodegradable poly（lactic-co-glycolic acid） （PLGA） microspheres by an oil-in-water emulsion solvent evaporation technique. In vitro characteristics and in vivo pharmacokinetics of RoMS were investigated. Results： The drug loading of rotigotine-loaded microspheres achieved by the optimized process was 27.0%, and the encapsulation efficiency was 90.2%. The average diameter of the particles was 71.5 μm. SEM analysis showed that the surface of the microspheres was spherical, smooth and nonporous. The in vitro drug release sustained for 14 days. Cmax was （6.27±1.32） ng？mL-1 at 96 h after the administration of rotigotine-loaded microspheres. It could be detected on 14th day after administration and the elimination was slow, which displayed continuous-release characteristics of rotigotine in rats. Conclusion： Rotigotine can be slowly released from the microspheres for 2 weeks in vivo as expected.