基于局部肿瘤药物与探针同步释放的纳米诊疗胶束的体外研究

In vitro study of theranostic micelles with synchronously released drugs and fluorescence probe for local tumor

目的以维生素E(VE)修饰的吉西他滨(GEM-VE)、VE修饰的紫杉醇(PTX-VE)为药物,以VE修饰的磺酰罗丹明B(SRB-VE)为荧光探针,以单甲氧基聚乙二醇外消旋聚乳酸乙醇酸共聚物(MPEG-PLGA)、聚乙二醇-维生素E嵌段共聚物(PEG-VE)、叶酸-聚乙二醇-维生素E(FA-PEGVE)分别为载体包载上述2种药物及探针,制备了3种纳米诊疗胶束并对其进行表征及体外释放试验。方法首先采用溶剂挥发法制备胶束,之后采用动态光散射法及透射电镜对纳米胶束进行表征,建立药物与探针的体外分析方法,最后研究药物及探针的体外释放度,并采用f2相似因子法对每种胶束中药物与探针的释放曲线进行拟合。结果制备的3种胶束为类球形或球形,MPEG-PLGA胶束的粒径为118.9 nm,PEG-VE胶束的粒径为95.58 nm,FA-PEG-VE胶束的粒径为96.93 nm,且均呈单峰分布;体外释放试验表明3种胶束中所包载的药物与探针可同步释放。结论所制备胶束分布均匀,体外分析方法准确可靠,体外释放的结果表明药物和探针达到了同步释放。

Objective To prepare and represent polyethylene glycol monomethyl oxygen radicals racemic polylactic acid ethanol acid copolymer （MPEG-PLGA）, polyethylene glycol-vitamine E copolymer （PEG- VE）, folate-polyethylene glycol-vitamine E copolymer （FA-PEG-VE） theranostic micelles entrapping gemcitabine decorated by vitamine E （GEM-VE）, paclitaxel decorated by vitamine E （PTX-VE）, sulforho- damine B decorated by vitamine E （SRB-VE）, and perform in vitro release study. Methods We prepared 3 micelles by solvent evaporation method, and dynamic light scattering and transmission electron microscope （TEM） were used to represent the prepared micelles. In vitro analytic methods were established and in vi- tro release study was performed by dynamic dialysis, and then f2 similarity factor was used to investigate the similarity of the release profiles of GEM-VE, PTX-VE and SRB-VE in micelles. Results The prepared micelles were spherical or similar spherical. The sizes of MPEG-PLGA micelle, PEG-VE micelle and FA- PEG-VE micelle were 118.9 nm, 95.58 nm, 96.93 nm, respectively, and the size distributions were all sin- gle peak. The release profiles of GEM-VE, PTX-VE and SRB-VE of 3 micelles were similar. Conclusion The prepared micelles are uniform, the in vitro analytic methods are accurate and reliable and the results of in vitro release prove that the drugs and the fluorescence probe could nearly be released synchronously.