目的 为解决白藜芦醇口服生物利用度低的问题，研制白藜芦醇二棕榈酰卵磷脂（DPPC）脂质粉雾剂。方法 采用薄膜分散法制备白藜芦醇DPPC脂质体，冷冻干燥得粉雾剂。采用正交试验设计优化处方，并对其粒径、包封率、电位、体外释放及肺部沉积进行研究。采用肉汤稀释法进行体外抗菌活性评价并测定最低抑菌浓度。结果 DPPC与胆固醇的质量比3：1、药物与DPPC的物质的量比1：3、水化时间15 min、甘露醇与DPPC质量比2：1制备得到白藜芦醇DPPC脂质粉雾剂，其包封率为（69.8±1.6）%，载药量为（2.4±0.9）%，粒径为（191.5±4.5）nm，Zeta电位为（12.4±1.5）mV。粉雾剂的空气动力学粒径为（3.2±0.2）μm，体外肺部沉积率为28.1%。对金黄色葡萄球菌、鲍曼不动杆菌、肺炎链球菌和铜绿假单胞菌进行体外抗菌活性评价，测得白藜芦醇原料药组对金黄色葡萄球菌、鲍曼不动杆菌、铜绿假单胞菌和肺炎链球菌均无抗菌活性，而白藜芦醇DPPC脂质粉雾剂组对金黄色葡萄球菌、鲍曼不动杆菌有抗菌活性，最低抑菌浓度分别为4.0、2.0 mg/mL。结论 制备的白藜芦醇DPPC脂质粉雾剂粒径小、分布均匀、稳定性良好，肺部沉积率高，体外对金黄色葡萄球菌和鲍曼不动杆菌有抗菌活性，有望成为替代传统抗生素治疗细菌性肺炎的有效制剂。

Objective To prepare the resveratrol-DPPC liposomal dry powder inhalations (RDLDPIs), and solve the problem of lower bioavailability of resveratrol after oral administration. Methods The RDLDPIs were prepared by film-dispersion and freeze drying. The formulation was optimized by orthogonal design. The particle size, entrapment efficiency, electric potential, in vitro release, and lung deposition were characterized. The broth microdilution method was used to evaluate the antibacterial activity and determine the minimal inhibitory concentration (MIC) in vitro. Results The optimized ratio of DPPC/cholesterol, resveratrol/DPPC, and mannitol/DPPC was 3:1, 1:3, and 2:1 in the prescription of RDLDPIs, respectively; And hydration time was 15 min. The entrapment efficiency of RDLDPIs was (69.8 ±1.6)%, the drug loading was (2.4 ±0.9)%, the particle size was (191.5 ±4.5) nm, and the zeta potential was (12.4 ±1.5) mV. The aerodynamic particle size of the powder was (3.2 ±0.2) μm and the in vitro pulmonary deposition ratio was 28.1% in vitro. The antibacterial activity against Staphylococcus aureus, Acinetobacter baumannii, Streptococcus pneumoniae, and Pseudomonas aeruginosa was evaluated in vitro. The crude drug group had no antibacterial activity in four species of bacteria, while RDLDPIs had antibacterial activity of Staphylococcus aureus and Acinetobacter baumannii, and MIC was 4 mg/mL and 2 mg/mL, respectively. Conclusion The prepared RDLDPIs have small size and uniform distribution with good stability and high lung deposition rate and in vitro antibacterial activity against Staphylococcus aureus and Acinetobacter baumannii, which is expected to be an substitute for traditional antibiotics for the treatment of bacterial pneumonia.

上海市卫生和计划生育委员会科研课题（20184Y0227）；上海市同济大学附属杨浦医院院级课题（Se1201601）