他克莫司类脂质体凝胶体内外经皮渗透性研究

In vitro/vivo transdermal permeation of tacrolimus niosomes gel

目的通过比较他克莫司(Tac)类脂质体(Tac-NS)凝胶、市售Tac软膏与普通凝胶的体内外经皮渗透性,阐明Tac-NS凝胶在提高Tac皮肤滞留量、延长药物释放的作用规律及特点。方法采用改良Franz扩散池进行离体猪皮渗透试验,以SD雄性大鼠为实验动物进行在体皮肤滞留研究,以LCMS/MS法测定接收液及皮肤中的Tac浓度,计算累积渗透量(Q)及皮肤滞留量(Q_(skin))。结果离体皮肤渗透试验中,Tac-NS凝胶在24 h内的Q_(skin)与Tac软膏相当(P>0.05),但明显高于普通凝胶(P<0.05);3种制剂的24 h累积渗透量(Q_(24))无明显差异(P>0.05)。大鼠在体皮肤滞留试验中,给药后8 h时的Tac-NS凝胶与Tac软膏Q_(skin)无明显差别(P>0.05),但12 h和24 h时,Tac-NS凝胶的Q_(skin)分别约为Tac软膏的2和2.5倍。结论 Tac-NS凝胶较普通(材料物理混合)凝胶可明显增加药物在离体及在体皮肤内的滞留量,与市售Tac软膏相比,Tac-NS能显著延长Tac在皮肤内的滞留时间,具有缓释作用。

Objective To compare the in vitro/vivo transdermal permeability of tacrolimus（Tac） niosomes（Tac-NS） gel, commercial Tac ointment and general gel, and to illuminate whether Tac-NS gel improves the retention and release of Tac. Methods Modified Franz diffusion cells were used in the in vitro transdermal permeation test. SD rats were used in the in vivo transdermal permeation test. The concentration of Tac in samples and skin was measured by LC-MS/MS. The cumulative penetration amounts（Q） and the cumulative retention amounts（Q_（skin）） were calculated. Results In the in vitro transdermal permeation test, the Q_（skin） of Tac-NS gel was similiar to that of Tac ointment（P 0.05） and higher than that of Tac-physical mixing gel（general gel）（P 0.05）. Q_（24） of Tac-NS gel was a little lower than that of Tac ointment and Tac-materials mixing gel but with no difference（P 0.05）. The in vivo transdermal permeation test showed that the Q_（skin） of Tac-NS and Tac ointment was similiar at 8 h. While the Q_（skin） of Tac-NS gel was 2 times and 2.5 times of that of Tac ointment at 12 h and 24 h（P 0.05）, respectively. Conclusion Compared with Tac ointment, Tac-NS gel increases the drug retention in the skin, indicating a sustained drug release character.