摘要
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100nm,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。
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.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2010年第19期1479-1483,共5页
Chinese Pharmaceutical Journal
基金
国家自然科学基金资助项目(30772665
30970785)
关键词
甲氧基聚乙二醇磷脂酰乙醇胺
全反式维甲酸
胶束
体外细胞抑制
methoxyl poly （ethylene glycol）-phosphatidylethanolamine
all-trans-retinoic acid
micelle
cell inhibition in vitro
