载地塞米松聚合物胶束的制备及其性质

Preparation and properties of dexamethasone-loaded polymer micelles

目的制备具有良好生物相容性的地塞米松聚合物胶束,为血管炎症提供一种高效的治疗方法。方法以聚己内酯-聚乙二醇载体和聚己内酯-聚甲基丙烯酸乙酯阳离子载体为材料制备地塞米松载药聚合物胶束。对所制备的载药聚合物胶束的形态、粒径、PDI、Zeta电位、包封率及载药量进行表征。以人脐静脉内皮细胞为细胞模型,采用噻唑蓝法考察载药胶束对HUVECs的细胞毒性并通过流式细胞术测定HUVECs对胶束的摄取情况。结果制备的载药胶束为椭球形,粒径约161 nm,Zeta电位为17.0±0.9 m V,包封率为83.87%±1.28%,载药量为15.06%±0.28%。为使载地塞米松胶束对细胞的毒性降到最低,其胶束浓度应不高于400μg·m L^(-1)。细胞摄取结果证实了阳离子载体具有加速细胞摄取的作用,当阳离子载体含量为50%时,其细胞摄取量为游离组的2.3倍。结论成功制备了相容性好且包封率高的地塞米松载药胶束,可加速药物进入内皮细胞,更好地达到治疗血管炎症的效果。

OBJECTIVE To preparation of dexamethasone-loaded polymer micelles with good biocompatibility,and thus to provide an efficient treatment method for the treatment of vascular inflammation.METHODS Polycaprolactone-polyethylene glycol carrier and polycaprolactone-polyethylmethacrylate cationic carrier were used as materials to prepared DXM-loaded polymer micelles.The morphology,particle size,PDI,Zeta potential,encapsulation efficiency and drug loading of the prepared dexamethasone-loaded polymer micelles were characterized.Human umbilical vein endothelial cells were used as cell model in cytotoxicity studies in vitro.Cytotoxicity of HUVECs was studied by MTT and uptake of the dexamethasone-loaded micelles by HUVECs was measured by flow cytometry.RESULTS The prepared dexamethasone-loaded micelles were ellipsoidal in shape and the particle size was 161 nm and Zeta potential was 17.0±0.9 m V.Entrapment efficiency was 83.87%±1.28%and drug loading was 15.06%±0.28%.In order to minimize the cytotoxicity of dexamethasone-loaded polymer micelles,the concentration of dexamethasone-loaded micelles should not be higher than 400μg·m L^(-1).The results of cell uptake studies showed that the cation carrier could accelerate the cell uptake.When cationic polymer content was 50%,the content of cell uptake was 2.3-fold more than that of the free group indicating a better uptake ability.CONCLUSION Dexamethasone-loaded micelles with good biocompatibility and high entrapment efficiency have been successfully prepared,which can accelerate the entry of dexamethasone into endothelial cells and achieve better therapeutic effect on vascular inflammation.