富勒醇/透明质酸脂质纳米载体的制备及氢醌透皮给药研究

目的：制备新型富勒醇/透明质酸脂质纳米载体（fullerol/hyaluronic acid hybrid lipidic nanocarriers，FHLNs），并用于氢醌（hydroquinone，HQ）的经皮给药研究。方法：采用薄膜分散法制备FHLNs，透射电镜观察粒子形态，马尔文粒度仪测定粒径和电位。用YB-P6型透皮仪研究FHLNs的体外透皮性能，并用模型拟合法评估FHLNs和游离HQ溶液的体外经皮渗透行为差异。结果：透射电镜结果显示FHLNs呈类球形。FHLNs的粒径为（180.10±1.00）nm，电位为（-35.13±0.32）mV。FHLNs的24 h累积经皮渗透量是游离HQ溶液的2.02倍。透皮实验结束时，FHLNs对离体鼠皮的刺激性明显弱于游离HQ溶液。模型拟合结果显示FHLNs和游离HQ溶液的经皮扩散模型均符合一级方程。FHLNs的透皮速率常数是游离HQ的2.30倍。结论：FHLNs能明显促进HQ的透皮吸收并减轻其皮肤刺激性。

Preparation of fullerol/hyaluronic acid hybrid lipidic nanocarrier and study on hydroquinone transdermal administration

OBJECTIVE To prepare a novel fullerol/hyaluronic acid hybrid lipidic nanocarriers (FHLNs) which was used for percutaneous administration of hydroquinone (HQ).METHODS FHLNs were prepared by thin film dispersion method. The particle morphology was observed by transmission electron microscopy. The particle size and potential were measured by Malvern particle sizer. The in vitro transdermal properties of FHLNs were studied by YB-P6 transilluminator, and the difference of in vitro permeation behavior between FHLNs and free HQ solutions was evaluated by model fitting method.RESULTS Transmission electron microscopy results showed that FHLNs were spherical particles. The particle size of FHLNs was (180.10±1.00) nm, the ζ potential was (-35.13±0.32) mV, and the encapsulation efficiency was (81.87±2.28) %. The 24-hour cumulative percutaneous penetration of FHLNs was was 2.02 times that of free HQ solution. After the transdermal experiment, FHLNs were observed to be significantly less irritating to isolated mouse skin than free HQ solution. The model fitting results showed that the diffusion models of FHLNs and free HQ were in accordance with the first-order equation. The transdermal rate constant of FHLNs was 2.30 times that of free HQ.CONCLUSION FHLNs can significantly promote the transdermal absorption of HQ and reduce its skin irritation.