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采用生物相容性聚合物胶束材料聚乙二醇-聚乳酸(mPEG-PLA)和普朗尼克P105(P105),构建了全新的混合胶束体系,用于提高难溶性麻醉药—丙泊酚的溶解度。相对于单纯由mPEG-PLA构建的载药胶束,该载药混合胶束能有效提高药物溶解度。最优化处方为mPEG-PLA:P105:丙泊酚=10:4:5(w/w/w),粒径约为90nm,多分散指数为0.2左右。载药混合胶束中游离药物浓度显著低于市售品脂肪乳(P<0.05)。此混合胶束于4oC条件下放置6个月,其粒径、多分散指数、游离药物浓度和载药量均无明显变化,说明4oC条件下该体系在6个月内是稳定的。混合胶束在各时间点的体外释放百分率显著高于市售品脂肪乳,这可能有利于更快发挥药效。睡眠/苏醒试验结果表明,混合胶束、单一胶束以及市售品脂肪乳的翻正反射消失时间和恢复时间没有显著性差异(P>0.05)。上述结果表明该混合胶束有望成为静脉给药系统应用于临床。
A novel mixed micellar system was constructed by using mPEG-PLA and Pluronic P105 (P105), a biocompatible polymer micellar material, to improve the solubility of propanol Solubility of phenol. Compared with the drug-loaded micelles constructed by mPEG-PLA alone, the drug-loaded micelles can effectively improve the drug solubility. The optimized formulation is mPEG-PLA: P105: Propofol = 10: 4: 5 (w / w / w) with a particle size of about 90 nm and a polydispersity index of about 0.2. Drug-loaded micelles free drug concentration was significantly lower than the commercially available fat emulsion (P <0.05). The mixed micelles placed at 4oC for 6 months, the particle size, polydispersity index, free drug concentration and drug loading did not change significantly, indicating that the system at 4oC at 6 months is stable. The percentage of in vitro release of the mixed micelles at each time point was significantly higher than that of the commercially available fat emulsion, which may be beneficial to the faster efficacy. Sleep / wake test results show that there is no significant difference (P> 0.05) in the disappearance time and the recovery time of the normal reflex of the mixed micelles, the single micelles and the commercial fat emulsions. The above results show that the mixed micelles are expected to become intravenous drug delivery system for clinical application.