维生素E琥珀酸酯修饰的普朗尼克P123胶束的初步研究

Preliminary investigation of Vitamin E succinate-modified P123 micelles

目的制备维生素E琥珀酸酯修饰的普朗尼克P123胶束,用以包载阿霉素,并对其进行表征和体外抗肿瘤活性评价。方法将维生素E琥珀酸酯修饰的普朗尼克P123接枝聚合物(P123-VES)通过透析法制备包载阿霉素的胶束体系,并对其粒径、电位、载药量、包封率、稳定性、药物释放等进行评价;考察该胶束体系对人乳腺癌MCF-7细胞肿瘤球生长的抑制效果。结果 P123-VES的临界胶束浓度为0.11μg·mL^(-1);载药胶束的粒径为108.40±0.46 nm,PDI为0.210±0.015,电位为-22.2±0.1 mV,载药量11.31±0.16%,包封率90.47±1.26%;载药胶束能在室温下稳定储存16 d以上;游离阿霉素在8 h内的累积释放率达97.34%,而载阿霉素胶束在48 h内的释放量仅约40%。对人乳腺癌MCF-7细胞3D肿瘤球的抑制效果为:载阿霉素胶束>阿霉素脂质体>盐酸阿霉素>对照组。结论文中制备的胶束大小适中且较为稳定,并有较好的体外抗肿瘤效果。

OBJECTIVE To prepare Vitamin E succinate-modified P123 micelles for Doxorubicin(DOX)delivery and to evaluate its in vitro anti-tumor effect.METHODS The Pluronic P123 modified with Vitamin E succinate was prepared micelles for DOX delivery by dialysis.The particle size,distribution,morphology,Zeta potential,storage stability,encapsulation efficiency,drug loading amount and release degree of DOX were measured.The effect of the DOX delivery system on growth inhibition of breast MCF-7 tumor spheroids was evaluated.RESULTS The Vitamin E succinate-modified P123 polymer was successfully prepared and its critical micelle concentration is 0.11μg·mL-1.For the DOX-loaded micelles,the particle size was 108.40±0.46 nm,PDI was 0.210±0.015,and Zeta potential was-22.2±0.1 mV.The drug loading and encapsulation efficiency were 11.31%±0.16%and 90.47%±1.26%,respectively.The micelles can maintain stable without aggregation or precipitation for 16 days.The cumulative drug release amount of free DOX reached 97.34%within only 8 h,while the release rate of drug-loaded micelles VP@DOX for 48 h was only about 40%.CONCLUSION The micelle system in this study was stable and possessed a suitable size for drug delivery to tumors,thus showing a good effect on anti-tumor.