利塞膦酸钠可溶性微针的制备及预防绝经后骨质疏松症研究

Fabrication of Risedronate Sodium-Loaded Dissolving Microneedles and Evaluation of Its Therapeutic Effects on Postmenopausal Osteoporosis

目的 制备利塞膦酸钠可溶性微针,对其进行表征及预防绝经后骨质疏松症药效评价。方法 通过响应面法优选微针的制备工艺;采用扫描电镜、皮内溶解试验、穿刺试验、皮肤屏障恢复试验与体外透皮试验对所制得微针的外观、溶解性能、机械性能、安全性、透皮特性进行表征;采用卵巢切除骨质疏松症模型大鼠进行药效学评价。结果 经过优选的微针配方为聚乙烯吡咯烷酮-硫酸软骨素(PVP K30-CS)配比为1∶0.86,溶剂占比55%;所得微针具有良好的性状,并展现出与口服给药相似的Ca^(2+)、P^(3+)和碱性磷酸酶(alkaline phosphatase,ALP)水平调节能力,显著提升模型大鼠骨密度并修复其骨微结构。结论 利塞膦酸钠可溶性微针质量稳定、使用方便、药效确切,是干预绝经后骨质疏松症的潜在选项。

OBJECTIVE To prepare risedronate sodium(RIS)-loaded dissolving microneedle(DMN) and evaluate its efficacy in preventing postmenopausal osteoporosis.METHODS The preparation process of RIS-DMN was optimized by Box-Behnken design of response surface methodology.The appearance,solubility,mechanical property,safety and transdermal effect of RIS-DMN were characterized by scanning electron microscope,intradermal dissolution test,puncture test,skin barrier recovery test and in vitro permeation test.The pharmacodynamic evaluation of RIS-DMN was performed in ovariectomized osteoporosis model rats.RESULTS The optimal formulation were determined to be 45% for solute(mixed with 1∶0.86 PVP K30 and CS) and 55% for solvent.It was found that the RIS-DMN have good physical characteristics and properties,and showed great effects in regulating the level of Ca~(2+),P~(3+)and alkaline phosphatase(ALP).Meanwhile,the RIS-DMN showed great effects in repairing bone microstructure and improving bone density in ovariectomized osteoporosis model rats,as similar as oral administration.CONCLUSION The RIS-DMN has stable quality,convenient use and precise efficacy,shows great potential in the treatment of postmenopausal osteoporosis.