环孢素A纳米粒滴眼液制备及眼的刺激性

Preparation of cyclosporine A nano-particle eye drops and its irritation to the eyes

背景:环孢素A可有效抑制角膜移植后的免疫排斥反应,但因难溶于水,不能配制成水溶性制剂用于眼局部。目的:制备1%环孢素A纳米粒滴眼液,并观察其眼刺激性。方法:采用聚乙二醇-聚乳酸共聚物对环孢素A药物进行包裹,制备浓度为1%的环孢素A纳米粒滴眼液,以透射电镜、激光粒度仪对制备的纳米粒子进行表征;通过家兔单次、多次给药眼刺激性实验观察环孢素A纳米粒滴眼液的眼刺激性。结果与结论:环孢素A纳米粒滴眼液包封率为85.10%,载药量为21.3%;纳米粒子为球形粒子,分散均匀;载药纳米粒子粒径分布较窄,粒径大小为(296.9±32.06)nm;体外释放曲线显示,环孢素A从纳米粒子中缓慢释放,20d左右释放量达总环孢素的91.3%。环孢素A纳米粒滴眼液单次、多次给药期间,家兔双眼结膜、角膜、虹膜的眼刺激性反应分值和综合评分均为0,说明其对眼无刺激性。

BACKGROUND： Cyclosporine A can inhibit the immunological rejection after corneal transplantation. But it cannot be formulated into ophthalmic solution for its insolubility. OBJECTIVE： To prepare 1% cyclosporine A nano-particte eye drops and to investigate its irritation to the eyes METHODS： Cyclospodne A was successfully incorporated into poty （ethylene glycol）-poly （dl-~actide） （PEG-PLA）, and 1% cyclosporine A nano-particle eye drops were prepared. The nano-particle eye drop was characterized by using transmission electron microscopy and dynamic light scattering. The irritation of cyclosporine A nano-particle eye drops was observed through single and multiple irritative tests to the eyes in rabbits. RESULTS AND CONCLUSION： Drug-loading and encapsulation efficiency of cyclosporine A nano-particle eye drops were 21.3% and 85.10%, respectively. The cyclosporine A nano-particles showed sphericity with even dispersion. The average size of cyclosporine A-loaded nano-particle was （296.9_＋32.06） nm with narrow distribution. Drug release curve in vitro exhibited a sustained drug release of cyclosporine A from the nano-particles. The release amount was 91.3% of cyclosporine A around 20 days. The irritation scores on the conjunctiva, cornea and iris were zero at the period of single and multiple administrations, indicating no irritation was found. These findings suggest that the cyclosporine A nano-particle has no irritation to the eyes.