利多卡因醇质体的理化性质及其皮肤刺激性研究

The Study of Physicochemical Properties and Skin Irritation of Lidocaine Ethosomes

目的:制备利多卡因醇质体,并对其理化性质及皮肤刺激性进行研究。方法:采用超声注入法制备利多卡因醇质体,使用透射电镜观察和激光粒度仪分析其形态、粒径大小及分布,采用透析法和HPLC法测定利多卡因醇质体的包封率,对不同温度下保存60天后的利多卡因醇质体的包封率进行测定以评估其稳定性,通过豚鼠皮肤刺激试验对利多卡因醇质体的皮肤刺激性进行分析。结果:利多卡因醇质体为圆形囊泡结构,粒径为31.33±2.63 nm,多分散指数为0.42±0.21,显示粒径分布较为均匀,其包封率为(52.85±0.36)%,保存在25±1℃时泄露最少,豚鼠完整及破损皮肤经利多卡因醇质体处理后均未见红斑和水肿反应,行组织学检查也未见明显炎症改变。结论:利多卡因醇质体具备理想的理化性质且对皮肤无刺激性,有望成为一种新型经皮局麻制剂。

Objective： To prepare the lidocaine ethosomes and investigate its physicochemical properties and skin irritancy.Methods： The lidocaine ethosomes was prepared by ultrasonic injection method. The morphology was examined by transmission electron microscope. The particle size and distribution were detected by Zetasizer instrument. The free drug was separated by dialysis method and the encapsulation efficiency of lidocaine ethosomes was determined by HPLC. The encapsulation efficiency at different temperatures was determined at sixtieth days to evaluate the stability. The guinea pigs were utilized to investigate the skin irritations of lidocaine ethosomes. Results： The lidocaine ethosomes was spherical vesicles, its size distribution was narrow with polydispersity index of 0.42 ±0.21, and its particle diameter and encapsulation efficiency were 31.33 ±2.63 nm and（52.85 ±0.36）%, respectively, the leakage of lidocaine ethosomes was lowest in storing at 25±1℃. There had no edema and erythema could be observed on the guinea pigs skin, and had no inflammation changes in the histopathological observation. Conclusion： The lidocaine ethosomes with ideal physicochemical properties has no skin irritation and is expected to be a new topical anaesthetic preparation.