何玲,许洪涛,聂淑芳,杨星钢,殷健,潘卫三
HE Ling1,XU Hong-tao1,NIE Shu-fang1,YANG Xing-gang1,YIN Jian2,PAN Wei-san1(1.School of Pharmacy

• 1:沈阳药科大学药学院
• 2:天津中医药大学中药学院

摘要(Abstract)：

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。
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.Conclusions 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.

关键词(KeyWords)： 氟比洛芬;阳离子脂质体;温敏凝胶;刺激性;药效学
flurbiprofen;cationic liposome;thermo-sensitive hydrogel;irritation;pharmacodynamics

Abstract:

Keywords:

基金项目(Foundation):

作者(Author): 何玲,许洪涛,聂淑芳,杨星钢,殷健,潘卫三
HE Ling1,XU Hong-tao1,NIE Shu-fang1,YANG Xing-gang1,YIN Jian2,PAN Wei-san1(1.School of Pharmacy

DOI: 10.14066/j.cnki.cn21-1349/r.2010.09.018

参考文献(References)：

• [1]LI Xiang,NIE Shu-fang,KONG Jun,et al.A controlled-release ocular delivery system for ibuprofen based onnanostructured lipid carriers[J].Int J Pharm,2008,363(1/2):177-182.
• [2]SRIVIDYA B,CARDOZA R M,AMIN P D.Sustainedophthalmic delivery of ofloxacin from a pH triggeredinsituhydrogelling system[J].J Control Release,2001,73(2):205-211.
• [3]LIN HR,SUNG K C,VONGW J.In situhydrogelling ofalginate/pluronic solutions for ophthalmic delivery of pi-locarpine[J].Biomacromolecules,2004,5(6):226-230.
• [4]THALLER V T,KULSHRESTHA M K,BELL K.Theeffect of pre-operative topical flurbiprofen or diclofenacon pupil dilatation[J].Eye,2000,14(4):642-645.
• [5]CHOI HG,JUNG J H,RYU J M,et al.Development ofin situ-hydrogelling and mucoadhesive acetaminophenliquid suppository[J].Int J pharm,1998,165(1):33-44.
• [6]LIU Zhi-dong,LI Jia-wei,NIE Shu-fang,et al.Study ofan alginate/HPMC-basedin situhydrogelling ophthalmicdelivery system for gatifloxacin[J].Int J Pharm,2006,315(1/2):12-17.
• [7]谢雷克,张俊杰,刘霞.复方牛磺酸眼药水消炎作用研究[J].眼科研究,1997,15(3):167-169.