降钙素葡聚糖颗粒缓释微球的研究

Research of SCT-Dextran Microspheres

目的:降钙素(一个由32个氨基酸组成的多肽)是治疗骨质疏松的首选药之一。降钙素的劣势是其半衰期过短,需要一天一次注射给药,本实验旨在制备突释小,药物释放浓度稳定的降钙素微球制剂。方法:制备降钙素羧酸葡聚糖颗粒和降钙素硫酸葡聚糖颗粒组合物,分别将其包裹于PLGA微球内,制备成降钙素组合微球,采用C18反相色谱柱研究药物的包封率和体外释放行为。结果:所制得的降钙素葡聚糖颗粒缓释微球体外释放一个月,释放曲线比较完美,接近零级释放。结论:本研究制得的降钙素葡聚糖颗粒缓释组合微球能实现理想的体外缓释效果,为后期药动学实验提供基础。

Objective： Salmon Calcitonin （sCT）, a small, 32-amino-acid peptide, secreted in response to excess calcium in serum, is one of the first choice for the treatment of osteoporosis. However, the therapeutic use of exogenously administered sCT is severely hampered by its rapid elimination from the body and short half-life （-43 min）, which in combination contribute to its poor and variable systemic bioavailability. We aimed to prepare sCT loaded sustained release microspheres without initial burst. Method： SCT and Dex-Sulfate were microencapsulated into PLGA microspheres by multiple emulsion technique. The encapsulation efficiency and vitro re- lease of microspheres were detected using HPLC system equipped with a C18 reverse column. Results： Sustained and constant release profiles were realized. Burst release rate of the first day was less than 10% of combined microsphere formulation. The 30-day cumulative release rate was up to 90%. Conclusions： SCT would achieve sustained release while encapsulated into PLGA microspheres, which pro- vided a basis for later pharmacodynamic study.