拉坦前列素脂质体滴眼液的眼表毒性

Ocular surface toxicity of latanoprost liposome eye drops

目的研究拉坦前列素(latanoprost,LAT)脂质体滴眼液对眼表的毒性。方法采用薄膜分散法制备拉坦前列素脂质体,平均粒径为(98.7±34.4)nm;采用随机数字表法将新西兰白兔15只分为3组,分别为Xalatan组、LAT Liposome组和无抑菌剂组,右眼给予试验滴眼液,左眼采用无菌生理盐水作为对照,1次/d给药,连续使用28 d;在每日给药前以及最后一次给药后的1、2、4、24、48、72 h进行眼刺激反应和角膜荧光素染色评分。结果 LAT Liposome组与无抑菌剂组在实验第28天刺激反应平均分值分别为0.96和2.24,属于无刺激,而Xalatan组评分值为4.17,属于轻度刺激;角膜荧光素染色实验中,给药后第21天,与对照组比较,Xalatan组评分开始显著升高(P<0.01);给药后第28天,与对照组比较,Xalatan组、无抑菌剂组评分均显著增加(P<0.01);与Xalatan组比较,LAT Liposome组评分显著降低(P<0.01),说明LAT Liposome对眼表刺激性最小,角膜损伤最轻。结论 LAT Liposome的毒性最小,更有利于长期使用。

Objective To investigate the ocular surface toxicity of latanoprost （LAT） liposome eye drops. Methods LAT liposome was prepared by thin-film ultrasonication method. The particle size of the liposome was （98. 7 ± 34. 4）nm. 15 Adult New Zealand rabbits were randomly divided into three groups respectively, Xalatan~ group,LAT liposome group and bacteriostat free group. The right eye of each animal was given test eye drops, and the left eye was administered with sterile physiological saline for 28 days once a day. Eye irritation and corneal fluorescein staining were performed daily before administration and after the last ad- ministration at 1,2,4,24,48,72 h. Results The average eye irritation scores of LAT liposome group and bacteriostat free group were 0.96 and 2.24 respectively on day 28, belonging to non-irritant; and Xalatan group was 4. 17, belonging to mild stimulation. In corneal fluorescein staining test, scores of Xalatan~ group were increased significantly（ P 〈 0. 01 ） compared with the control group after administration of 21 d; scores of Xalatan~ group and bacteriostat free group were both increased significantly （P 〈 0. 01 ） compared with the control group after administration of 28 d; comparing with Xalatan~ group, scores of LAT liposome group decreased significantly（ P 〈 0. 01 ）. The test results showed that LAT liposome eye drops having smal- lest irritation and lightest corneal injury. Conclusions LAT liposome with minimal toxicity is more suitable for long time use.