离体皮肤渗透法测定三七总皂苷传递体经皮吸收特性

目的确立离体皮肤渗透法测定三七总皂苷(PNS)传递体中药物经皮吸收的主要条件并初步阐明载体中药物的经皮吸收特性。方法采用薄膜分散法制备PNS传递体和脂质体,并对其进行理化性质表征;筛选离体皮肤渗透试验中PNS传递体的合适药物用量与上样量;考察不同载体(传递体和脂质体)类型、传递体的粒径及处方中脱氧胆酸钠(DOC)的量对PNS经皮渗透的影响。结果 PNS传递体和脂质体均为近似球形的单层囊泡,粒径分别为(121.2±4.5)、(113.9±2.9)nm,无聚集现象。根据药物皮肤累积透过量(Qn)与稳态经皮渗透速率(J)的测定值,将传递体药物用量确定为500 mg,上样体积定为0.5 m L。PNS中各被测成分(人参皂苷Rg1、人参皂苷Rb1、人参皂苷Re和三七皂苷R1)的皮肤Qn传递体均高于脂质体,各被测成分的J前者为后者的2~3倍。粒径120 nm的PNS传递体与粒径250 nm的PNS传递体相比各被测成分在各取样点的皮肤Qn与J均要高。与含DOC量低的传递体相比,含DOC量高的传递体的皮肤Qn与J均明显增大,不同成分增大的倍数有一定差异。结论离体皮肤渗透法可用于测定PNS传递体中药物的经皮吸收特性,传递体促进药物经皮渗透的作用明显强于脂质体,传递体粒径相对较小,其中DOC用量适当增加均有利于药物经皮渗透。

Determination of percutaneous absorption characteristics of Panax notoginseng saponins transfersomes by in vitro skin permeation method

Objective To establish the key conditions for the determination of percutaneous absorption of Panax notoginseng saponins (PNS) in transfersomes (TFS) by in vitro skin permeation method and clarify its percutaneous absorption characteristics. Methods The film hydration-dispersion method was used to prepare PNS TFS and liposomes (LPS). Their physico-chemical properties were characterized. The drug content and sample volume of PNS TFS for in vitro skin permeation experiments were screened. The effects of vesicle type (TFS or LPS), size of the TFS, and formulation amount of sodium deoxycholate (DOC) on percutaneous permeation of PNS were investigated. Results The TFS and LPS were mainly unilamellar vesicles with roundish shape and size of (121.2 ± 4.5) and (113.9 ± 2.9) nm, without gathering property. According to the cumulative permeated quantity (Q_n) and steady-state percutaneous permeation rate (J) of the assayed ingredients, the appropriate PNS content in the TFS was 500 mg and sample volume was 0.5 mL. Compared with those of the LPS, the Q_n values of each assayed component (ginseng saponin Rg₁, ginseng saponin Rb₁, ginseng saponin Re, PNS R₁) in PNS of the TFS were high, and the J values of the assayed components in TFS were about 2-3 times of those in the LPS. The Q_n and J values of the assayed components in the TFS with an average size of 120 nm were obviously higher than those of the assayed components in the TFS with an average size of 250 nm. The Q_n and J values of the assayed components in PNS TFS with large amount of DOC were prominently higher than those containing small amount of DOC, and the increase ratios of different assayed components were different. Conclusion In vitro skin permeation method is suitable for the determination of percutaneous absorption of PNS in TFS. The TFS promote drug percutaneous permeation stronger than the LPS and the promotion increases with an appropriate increase of the amount of DOC and decrease of vesicle size of the TFS.