TMC60包衣的INS阳离子纳米脂质体-原位凝胶眼球滞留性及刺激性研究

Study on corneal retention and irritation behavior of N-trimethyl chitosan-coated insulin nanoliposomal in-situ gels

目的选用胰岛素(INS)为主药,制备N-三甲基壳聚糖(TMC)包衣INS阳离子纳米脂质体-原位凝胶(ISG),并对其在家兔角膜滞留性及眼刺激性进行研究。方法采用逆向蒸发法制备TMC60包衣INS纳米脂质体(INSL),并与等体积25%的泊洛沙姆溶液混匀制成眼用阳离子纳米脂质体-原位凝胶(TMC60-INSL-ISG);采用悬挂泡技术和束缚泡技术进行离体眼球表面接触角及解吸附动力学研究;以Draize评分法评价其对兔角膜的刺激性。结果 INSL-ISG粒径分布均匀,TMC60包衣后荷正电性;TMC60-INSL-ISG对家兔角膜无刺激性,与各参比制剂相比,TMC60-INSL-ISG在角膜表面接触角明显降低,解吸时间明显延长。结论 TMC60-INSL-ISG兼具阳离子纳米脂质体及原位凝胶的优势,可明显延长角膜滞留时间,且不会对眼部造成刺激性,值得进一步研究。

Objective To prepare insulin （INS）-loaded cationic nanoliposomal in-situ gels （ISG） with N-trmiethyl chitosan （TMC60） coating and investigate the corneal retention and irritation behavior in rabbit eyes. Methods Insulin-loaded nanoliposomes （ INSL） were prepared by a reverse evaporation method followed by TMC60-coating to obtain TMC60-coated INSL. Insulin （INS）-loaded cationicnano- tiposomal in-situ gels（TMC60-INSL-ISG） were prepared by mixing TMC60-coated INSL with an equal volume of 25% Poloxamer407. The contact angle and corneal retention behavior were evaluated by sessile bubble technique and captive bubble technique. Ocular irritation test was carried out based on the Draize method. Results INSL-ISG was uniformly distributed with positive surface charge after TMC60 coating. TMC60-INSL-ISG showed little corneal irritation and exhibited smaller contact angle and longer corneal retention time compared with the reference preparations. Conclusion TMC60-coated INSL-ISG has advantages of cationic nanoliposomes and in-situ gels with prolonged corneal retention time and little corneal irritation, which deserves further study.