兔曲霉菌性角膜溃疡局部应用两性霉素B脂质体的研究

目的 探讨兔曲霉菌性角膜溃疡局部应用两性霉素B脂质体(Liposomal amphotericin B,LAmB)和两性霉素B(AmB)滴眼液后,角膜及房水中的药物代谢状况。方法 用105只新西兰白兔,随机分为5组,采用角膜“#”形划痕法制作兔实验性曲霉菌性角膜溃疡模型,分别应用0.5% LAmB、0.25% LAmB、0.5% AmB点眼,分别在用药后5 min、15 min、30 min、1 h、2 h、4 h、8 h,共7个时点,抽取兔眼房水并取下角膜,用高效液相色谱检测(high performance liquid chromatography,HPLC)测定角膜及房水中两性霉素B的药物浓度。结果 三组滴眼液在7个时间点角膜中的药物浓度均能超过MIC₉₀;在房水检测中,0.5%AmB滴眼液组房水中的药物浓度超过MIC₉₀时段在用药30 min后至2 h之间,而0.5% LAmB,0.25% LAmB滴眼液组在用药15 min后房水中的药物浓度分别达到(10.57±0.042)μg/mL和(7.55±0.170)μg/mL,8 h后仍能维持在MIC₉₀以上,药物浓度分别为(5.344±0.3673)μg/mL和(4.382±0.3591)μg/mL。结论 LAmB滴眼液具有较好的缓释作用和生物利用度,药物浓度稳定,作用时间长,0.25%LAmB滴眼液是局部治疗曲霉菌性角膜溃疡的合适浓度。

Application of amphotericin B liposomes to aspergillus corneal ulcer in rabbits

Objective Explore the effect of amphotericin B liposome (LAmB)and amphotericin B (AmB) eye drops on rabbit aspergillus corneal ulcer from the drug concentration in cornea and aqueous humor.Methods 105 New Zealand white rabbits were selected in study,and divided into 5 groups randomly.Make rabbit aspergillus corneal ulcer models with “#” form scratch,0.5% LAmB,0.25%LAmB,0.5%AmB eye drops were used respectively.5 min,15 min,30min,1 h,2 h,4 h and 8 h after the use of eye drops were selected as the study points.High-performance liquid chromatography(HPLC) was used to detect the drug concentration of amphotericin B in the cornea and aqueous humor.Results In the cornea,the drug concentration exceed MIC₉₀ in seven point of the three groups; In aqueous humor detection,the drug concentration(μg/mL) more than MIC₉₀ period in 0.5%AmB eye drops group between 30 minutes to 2 hours,and 0.5%LAmB,0.25%LAmB eye drops group from 15 minutes (10.570.042) μg/mL and (7.550.170) μg/mL respectively to 8 hours (5.3440.3673) μg/mL and (4.3820.3591) μg/mL respectively.Conclusion LAmB eye drops has superior slow release effect,bioavailability,stable drug concentration and lasting effect; 0.25%LAmB eye drops is the suitable concentration in local treatment of aspergillus corneal ulcer.