Department of Pharmacy, 1st Hospital of Lanzhou University, Lanzhou, 730000, China.
AAPS PharmSciTech. 2010 Sep;11(3):1350-8. doi: 10.1208/s12249-010-9509-6. Epub 2010 Aug 26.
A novel transmembrane pH gradient active loading method to prepare alkaloids binary ethosomes was developed in this work. Using this novel method, binary ethosomes containing total alkaloids extracted from Sophora alopecuroides (TASA) were prepared successfully at the temperature below the phase transition temperature (Tc) of the phosphatidyl choline (PC). Several factors affecting this method were investigated. The qualities of the TASA binary ethosomes were characterized by the shape, particle size, and encapsulation efficiency (EE). The percutaneous absorption study of TASA binary ethosomes was performed using confocal laser scanning microscopy and Franz diffusion cells. The results showed that more than 90% sophoridine, 47% matrine, 35% sophocarpine, and 32% lemannine in TASA were entrapped within 1 h at 40°C, with an efficiency improvement of 8.87, 8.10, 7.63, and 7.78-fold than those observed in passive loading method. Transdermal experiments showed that the penetration depth and fluorescence intensity of Rhodamine B from binary ethosome prepared by pH gradient active loading method were much greater than that from binary ethosome prepared by passive loading method or hydroalcoholic solution. These results suggested transmembrane pH gradient active loading method may be an effective method to prepare alkaloids ethosomal systems at the temperatures below the Tc of PC.
本工作开发了一种新颖的跨膜 pH 梯度主动载药法，用于制备生物碱二元醇质体。利用该新方法，在磷脂酰胆碱（PC）相变温度（Tc）以下的温度下成功制备了含有苦参总碱（TASA）的二元醇质体。考察了影响该方法的多种因素。采用形态学、粒径和包封效率（EE）对 TASA 二元醇质体的性质进行了表征。采用共聚焦激光扫描显微镜和Franz 扩散池进行了 TASA 二元醇质体的经皮吸收研究。结果表明，在 40°C 下 1 h 内，TASA 中超过 90%的槐定碱、47%的苦参碱、35%的氧化苦参碱和 32%的氧化槐果碱被包封，包封效率分别提高了 8.87、8.10、7.63 和 7.78 倍，优于被动载药法。透皮实验表明，跨膜 pH 梯度主动载药法制备的二元醇质体中 Rhodamine B 的穿透深度和荧光强度明显大于被动载药法或醇水溶液制备的二元醇质体。这些结果表明，跨膜 pH 梯度主动载药法可能是在低于 PC Tc 的温度下制备生物碱醇质体系统的有效方法。
