Taymouri Somayeh, Varshosaz Jaleh, Hassanzadeh Farshid, Haghjooy Javanmard Shaghayegh, Dana Nasim
Department of Pharmaceutics, School of Pharmacy and Novel Drug Delivery Systems Research Centre, Isfahan University of Medical Sciences, Isfahan, Iran.
Department of Medicinal Chemistry, School of Pharmacy, Isfahan University of Medical Sciences, Isfahan, Iran.
IET Nanobiotechnol. 2015 Oct;9(5):306-13. doi: 10.1049/iet-nbt.2014.0076.
Polymeric micelles (PMs) were formulated as nano carriers for docetaxel intended for both intravenous administration and improve therapeutic efficacy of the drug. The PMs were formulated using folic acid conjugated Synpronic F127-cholesterol copolymer and were optimised using a 2(3) full factorial design. The effects of different formulation variables were evaluated on the particle size, entrapment efficiency (EE), zeta potential and release efficiency of the micelles. The in vitro cytotoxicity of DTX-loaded FA targeted micelles was studied on B16F10 melanoma cells which over expressed FA receptor. Among the studied single factors, solvent type was the most effective parameter on the EE and release efficiency. Polymer/drug ratio had the most considerable effect on the particle size while, zeta potential was more affected by temperature. Finally, the PMs with polymer/drug ratio of 12 prepared at 25°C by dimethyl sulfoxide as the dialyzing solvent was shown to be the optimum formulation with desirability factor of 84.9%. The optimised formulation exhibited a particle size of 171.3 nm, 99.59% drug EE, zeta potential of -7.80 mV, drug release efficiency of about 70% at 144 h and polydispersity index of 0.32. The MTT assay indicated DTX-loaded FA targeted micelles were significantly more cytotoxic than non-targeted micelles and free drug.
聚合物胶束（PMs）被制备成多西他赛的纳米载体，用于静脉给药并提高该药物的治疗效果。这些PMs是使用叶酸共轭的泊洛沙姆F127 - 胆固醇共聚物制备的，并采用2(3)全因子设计进行优化。评估了不同制剂变量对胶束的粒径、包封率（EE）、zeta电位和释放效率的影响。研究了负载多西他赛的叶酸靶向胶束对过表达叶酸受体的B16F10黑色素瘤细胞的体外细胞毒性。在所研究的单因素中，溶剂类型对EE和释放效率是最有效的参数。聚合物/药物比例对粒径影响最为显著，而zeta电位受温度影响更大。最后，以二甲基亚砜作为透析溶剂，在25°C下制备的聚合物/药物比例为12的PMs被证明是最佳制剂，可取性因子为84.9%。优化后的制剂粒径为171.3 nm，药物EE为99.59%，zeta电位为 -7.80 mV，在144小时时药物释放效率约为70%，多分散指数为0.32。MTT试验表明，负载多西他赛的叶酸靶向胶束的细胞毒性明显高于非靶向胶束和游离药物。
