目的 制备白藜芦醇脂质体（resveratrol-liposomes，Res-Lip），并考察经鼻腔给药的药动学行为。方法 通过单因素考察氢化大豆卵磷脂（HSPC）与胆固醇质量比、药脂比、药物含量、超声功率及超声时间对Res-Lip的粒径和包封率的影响，优化处方，以得到粒径分布均匀、稳定的Res-Lip。采用LC-MS/MS测定大鼠经鼻腔给药的血药浓度，初步评价Res-Lip在大鼠体内的药动学特征。结果 采用薄膜分散法，以HSPC与胆固醇质量比为3∶1、药脂比为1∶16、药物含量为30 mg、超声功率为550 W、超声时间为6 min制备的脂质体平均粒径为（75.25±0.33）nm，ζ电位为（-33.80±0.74）mV，包封率达到（92.94±0.32）%。Res-Lip经鼻腔给药后，相比于口服给药，药物清除半衰期（t_1/2）提高了2.11倍，最大血药浓度（C_max）提高了1.94倍，滞留时间延长2.42倍。结论 使用薄膜分散法制备的Res-Lip，能有效增强白藜芦醇的稳定性与溶解度，提高其在体内的生物利用度，为白藜芦醇新剂型的开发具有一定的参考价值。

Objective To prepare resveratrol-liposomes (Res-Lip), and study its the pharmacokinetics behavior by intranasal administration. Methods The effects of hydrogenated soy phosphatidylcholine (HSPC)-cholesterol ratio, drug-lipid ratio, drug content, ultrasounic power and ultrasound time on the particle size and encapsulation efficiency of Res-Lip were investigated by single factor test. The prescription was optimized to obtain uniformly distributed and stable of Res-Lip. The blood concentration of Res-Lip administered nasally to rats was determined by LC-MS/MS, and the pharmacokinetic characteristics of Res-Lip were evaluated in vivo in the preliminary study. Results The average particle size of liposomes was (75.25 ±0.33) nm, the ζ potential was (−33.80 ±0.74) mV, and the encapsulation rate reached (92.94 ±0.32)% using the thin film dispersion method with HSPC-cholesterol ratio of 3∶1, drug-lipid ratio of 1∶16, drug content of 30 mg, ultrasounic power of 550 W, and ultrasound time of 6 min. Res-Lip administered nasally resulted in a 2.11-fold increase in t_1/2, a 1.94-fold increase in C_max, and a 2.42-fold prolongation of retention time compared to oral administration. Conclusion The Res-Lip prepared by the film dispersion method can effectively enhance the stability and solubility of resveratrol, and improve its bioavailability in vivo, which has certain reference value for the development of new formulation for resveratrol.

R283.6

国家自然科学基金资助项目（82260816）;江西省自然科学基金资助项目（20202BAB216038）;江西省自然科学基金资助项目（20202ACB206011）;江西中医药大学博士启动基金（2018WBZR001）;国家中医药管理局“青年岐黄学者”培养计划（2022256）;江西中医药大学大学生创新创业训练.计划项目（X202310412222）