目的 制备并优化含聚乙二醇1000维生素E琥珀酸酯(TPGS)的秋水仙碱醇质体,并考察其作为秋水仙碱经皮给药载体的可行性。方法 采用注入超声法制备含TPGS秋水仙碱醇质体,微柱离心法测定包封率,并以包封率为评价指标,采用均匀设计试验优化该醇质体处方,并考察其理化性质;采用Franz扩散装置比较含TPGS秋水仙碱醇质体与普通秋水仙碱醇质体、秋水仙碱30%乙醇溶液的透皮性能。结果 优化的含TPGS秋水仙碱醇质体处方为秋水仙碱20 mg、大豆磷脂350 mg、TPGS 50 mg、乙醇体积分数为36.44%。按优化后处方制得的含TPGS秋水仙碱醇质体的平均包封率为(74.71±2.18)%,粒径为(89.6±3.5)nm,多分散指数为0.201±0.008,Zeta电位为(-34.6±2.7)mV。体外透皮实验中普通秋水仙碱醇质体的累积渗透药量为(64.49±5.61)μg/cm²,稳态透皮速率为(2.84±0.23)μg/(cm²·h),皮内滞留量为(128.22±11.64)μg/cm²;而含TPGS秋水仙碱醇质体的累积渗透药量为(91.36±7.11)μg/cm²,稳态透皮速率为(4.73±0.38)μg/(cm²·h),皮内滞留量为(182.84±14.37)μg/cm²,均明显高于普通秋水仙碱醇质体。结论 含TPGS秋水仙碱醇质体包封率高,促进秋水仙碱透皮吸收效果明显,有望成为秋水仙碱经皮给药的新载体。

Objective To prepare and optimize the prescription of colchicine ethosomes containing D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and to investigate its feasibility as a carrier for transdermal drug delivery. Methods The colchicine ethosomes containing TPGS were prepared by the injection-sonication method. And the encapsulation efficiency (EE) was determined by minicolumn centrifugation method. The prescription of ethosomes was optimized by uniform design with EE as the evaluation index, and the physicochemical properties of the optimized ethosomes were investigated. Characterization of the vesicles was based on particle size, Zeta potential, entrapment efficiency, and transmission electron microscopy (TEM). The transdermal permeation characteristics of ethosomes, colchicine 30% ethanol solution, and colchicine ethosomes containing TPGS were compared by using Franz diffusion cells. Results The optimized formulation was as follows: The contents of soybean phospholipid and TPGS were 350 and 50 mg, respectively. In addition, the concentration of ethanol was 36.44%. The average EE, particle size, polydispersity index, and Zeta potential were (74.71 ± 2.18)%, (89.6 ± 3.5) nm, 0.201 ± 0.008, and (-34.6 ± 2.7) mV, respectively. The in vitro experiment showed that the transdermal flux, permeation rate, and skin deposition of colchicine ethosomes were (64.49 ± 5.61) μg/cm², (2.84 ± 0.23) μg/(cm²·h), (128.22 ± 11.64) μg/cm², and the transdermal flux, permeation rate, and skin deposition of colchicine ethosomes containing TPGS were (91.36 ± 7.11) μg/cm², (4.73 ± 0.38) μg/(cm²·h), and (182.84 ± 14.37) μg/cm², respectively, which was significantly higher than those in ethosomes. Conclusion The colchicine ethosomes containing TPGS show high EE and obviously enhance the percutaneous absorption of colchicine, which might be a potential carrier for transdermal drug delivery.

江苏省“333高层次人才培养工程”科研专项(2011III-2651)