维甲酸/聚乙二醇磷脂酰乙醇胺胶束的制备及优化

 目的 制备甲氧基聚乙二醇磷脂酰乙醇胺（mPEG-DSPE）两亲线型聚合物及其载全反式维甲酸（ATRA）的胶束,通过考察胶束的电位、粒径、包封率进行制备工艺的优化。方法 选择多种制备方法及不同药物/聚合物比例制备ATRA胶束。用荧光探针技术测定临界胶束浓度（CMC）,动态光散射（DLS）法测定其粒径及电位,紫外分光光度法对胶束的载药等性质进行表征,Sulforhodamine B（SRB）法考察载药聚合物胶束及游离ATRA对Balb/c脑内皮细胞的抑制作用。结果 药物/聚合物比例对胶束粒径及包封率的影响显著,在药物/聚合物的比例为1∶20时,胶束的粒径约为100 nm,包封率为17.47%。mPEG-DSPE聚合物载ATRA胶束可以明显增加ATRA在水中的溶解度,抑制细胞生长的能力约为游离ATRA 的29倍。结论 两亲性聚合物mPEG-DSPE的胶束对疏水药物ATRA有良好的装载能力,可以显著增加ATRA的溶解度,聚合物胶束能增强ATRA体外细胞毒作用。

Preparation and Optimization of ATRA Loaded mPEG-DSPE Polymer Micelles

OBJECTIVE To prepare all-trans-retinoic acid (ATRA) loaded methoxyl poly(ethylene glycol)-phosphatidylethanolamine (mPEG-DSPE) amphiphilic linear polymer micelles and characterize their ζ potential, size and loading efficiency for optimizing preparation process. METHODS ATRA loaded micelles with different drug/polymer ratio were prepared by series methods. The critical micelle concentration (CMC) of the mPEG-DSPE polymer was estimated to prove the potential of micellar structure formation using fluorescence spectroscopy. Dynamic light scattering (DLS) was performed to measure the micelles size and ζ potential. The drug loading efficiencies were investigated with UV spectrophotometry. Sulforhodamine B (SRB) was used to investigate cell inhibition of drug-loaded polymeric micelles and free drugs. RESULTS Size and drug loading efficiency of micelles were affected by preparation method and drug/polymer ratio remarkably. The micelles had 100 nm in size and 17.47% in drug loading efficiency in the appropriate preparation condition with the ratio of drug to polymer of 1∶20. The ability to inhibit cell growth of drug-loaded polymeric micelles was about 30 times as that of free ATRA. CONCLUSION The amphiphilic linear polymer of mPEG-DSPE could effective load hydrophobe of ATRA. The ATRA loaded mPEG-DSPE micelles showed obviously solubility cytotoxicity enhancement in vitro.