目的 研制灵芝三萜纳米混悬凝胶剂（GT-NS-gel），并进行体外透皮研究。方法 采用高压均质法制备灵芝三萜纳米混悬剂（GT-NS），然后进一步制成凝胶剂。以24 h体外累积释放率和24 h后皮肤中的滞留量为指标，通过效应面法优化GT-NS-gel的处方；比较优化后的GT-NS-gel和灵芝三萜凝胶剂（GT-gel）的体外经皮渗透量及滞留量。结果 以最优处方：5 mg/g卡波姆940、30 mg/g GT、47.2 mg/g卵磷脂制得的GT-NS-gel在24 h时的体外累积释放率为（56.28±2.16）%，24 h皮肤滞留量为（472.89±8.74）μg/cm²，理论预测值与实测值接近，模型具有良好的预测性；GT-NS-gel 24 h药物累积渗透量和皮肤滞留量分别为（50.73±4.97）和（475.89±10.74）μg/cm²，明显高于GT-gel的（14.79±3.45）和（101.32±7.02）μg/cm²（P<0.05）。结论 将灵芝三萜制成纳米混悬凝胶剂，能够增加药物的皮肤滞留量，提高药物在皮肤局部的生物利用度。

Objective To prepare the nanosuspension-based gel of Ganoderma lucidum triterpenoids (GT-NS-gel) and investigate the in vitro transdermal diffusion characteristics. Methods GT-NS was prepared by high pressure homogenization and then transformed into gel. The formulation of GT-NS-gel was optimized by response surface method with cumulative release of drug from the GT-NS-gel within 24 h, and the amount of drug in the skin after applying GT-NS-gel for 24 h was used as indexes. In vitro percutaneous permeation and skin deposition of GT-NS-gel were studied and compared with those of GT-gel. Results The GT-NS-gel prepared by optimal formulation (5 mg/g Carbomer 940, 30 mg/g GT, and 47.2 mg/g lecithin) could release in vitro at 24 h to (56.28 ± 2.16)%, and the amount of drug in the skin after applying GT-NS-gel for 24 h was (472.89 ± 8.74) μg/cm². There was a little deviation between the theoretically predicted value and the measured value. It showed that this model had a good prediction. The amounts of GT penetrating through the skin and in the skin after applying GT-NS-gel for 24 h were (50.73 ± 4.97) and (475.89 ± 10.74) μg/cm², which were significantly higher than GT-gel (P < 0.05). Conclusion The GT-NS-gel has the ability to increase drug concentration in the skin, which can improve the bioavailability of the local skin.

家新药创制重大专项（2014ZX09J14106-01A）;北京市自然科学基金资助项目（7122176）