氟比洛芬阳离子脂质体温敏凝胶滴眼剂的眼部刺激性和药效学

目的制备氟比洛芬阳离子脂质体温敏凝胶滴眼剂(flurbiprofen cationic liposome thermo-sensitive hydrogel,FCLTH),考察其包封率、胶凝性质、眼部刺激性和药效作用。方法采用乙醇注入-超声法制备氟比洛芬阳离子脂质体,并对其包封率和理化性质等进行了测定。将氟比洛芬阳离子脂质体制备成温敏凝胶滴眼液,考察了FCLTH的胶凝行为、眼部刺激性和药效学。结果氟比洛芬阳离子脂质体包封率可达(84.9±2.75)%,zeta电位为(+33.4±9.68)mV,平均粒径(136±2.98)nm。FCLTH胶凝温度为31.9℃。眼部刺激性实验多次给药后,裂隙灯显微镜观察新西兰兔眼角膜无混浊,虹膜和结膜未见红肿、充血、肿胀等异常现象。组织病理学检查显示,新西兰兔眼7天多次给药后,与空白溶剂相比,给药组组织病理学改变无明显差异。药效学结果显示,FCLTH相对于氟比洛芬滴眼剂对新西兰兔眼急性炎症有抑制作用更强。结论采用乙醇注入-超声法制备的氟比洛芬阳离子脂质体有较高的包封率,且FCLTH在眼部温度下自发形成凝胶,无眼部刺激性,并能够有效抑制眼部炎症作用。

Irritation and pharmacodynamics study on flurbiprofen cationic liposome thermo-sensitive hydrogel for ocular delivery

Objective　To study the entrapment efficiency，gelation behavior，ocular irritation and pharmacodynamics of flurbiprofen cationic liposome thermosensitive hydrogel(FCLTH). Methods　The flurbiprofen cationic liposome was prepared using the ethanol injection-ultrasonic method and the entrapment, particle size and zeta potential were determined. Irritation and pharmacodynamics of FCLTH were studied. Fifteen rabbits were randomly divided into two groups for the study of irritation and pharmacodynamics. Six rabbits out of them were divided randomly into such two subgroups as FCLTH and blank cationic liposome thermo-sensitive hydrogel were used to study the irritation; other rabbits were divided randomly into such three subgroups as FCLTH, flurbiprofen eye drops (positive control) and normal saline, for the pharmacodynamics study. The rabbits were observed periodically for ocular redness, swelling, and watering with slit lamp microscope. Results　The entrapment efficiency of the flurbiprofen cationic liposome suspension (FCLS) was approximately (84.9±2.75)% with an average particle size of (136±2.98) nm and zeta potential(+33.4±9.68) mV. The gelatinization temperature of the optimized suspension was approximately 31.9 ℃. Histopathologic examination also revealed that there was no significant difference between rabbit eyes that administratered with the FCLTH and the ones which treated with blank cationic liposome thermo-sensitive hydrogel. No ocular damage or abnormal clinical signs of the cornea, iris or conjunctivae were observed. So it indicated that the formulations were nonirritating. Pharmacodynamic study also showed that the FCLTH was more effective in reducing ocular inflammation than the contrast eye drops. Conclusion The flurbiprofen cationic liposome is prepared using the ethanol injection-ultrasonic, which can improve the entrapment efficiency. FCLTH can transfer into hydrogel in the body temperature, cause no irritation. It has a beneficial effect for ocular delivery of certain irritable drugs.