叶黄素纳米粒原位凝胶滴眼剂的制备与体外评价

Preparation and in Vitro Evaluation of Eye Drops of In-situ Gel Loaded with Lutein Nanoparticles

目的制备叶黄素纳米粒离子敏感型眼用原位凝胶滴眼剂,并对其进行体外评价。方法采用超声辅助反溶剂沉淀法制备叶黄素白蛋白纳米粒,加入去乙酰结冷胶进一步制得离子敏感型原位凝胶;pH计与流变仪分别测定其与人工泪液混合前后的pH值及流变学特征;采用桨法考察制剂体外释放行为。结果制备的叶黄素纳米粒粒径为(114.93±8.64)nm,冻干后粒径增大但仍分布均匀;所得叶黄素纳米粒凝胶液的实际载药量为(0.686±0.05)mg·g-1。与人工泪液混合后形成持水性良好的凝胶,人工泪液混合前、后凝胶样品的p H分别为(7.09±0.14)和(7.34±0.33);体外累积释放率在10h时达到80%。结论将叶黄素纳米粒载入离子型凝胶材料中所得的原位凝胶在生理条件下发生胶凝,黏附性能增加且具有缓释作用。

Objective The eye drops of ion-sensitive in-situ gel loaded with lutein nanoparticles was prepared and evaluated in vitro. Methods Lutein albumin nanoparticle was prepared by ultrasound-assisted anti-solvent precipitation method. Eye drops of ion-sensitive in-situ gel loaded with lutein nanoparticles was prepared with gellan gum as ion sensitive polymer materials. The pH and rheological behavior before and after mixed with artificial tears were determined by pH meter and rheometer. Paddle method was adopted to investigate in vitro release profile of the drug-loaded gel. Results The particle size of obtained lutein nanoparticles was（114.933±8.64）nm,and increased after freeze-drying but still with uniform size distribution.Drug loading of the gel was（0.686±0.05）mg·g^-1,and it formed gel after mixed with artificial tears. The p H value of artificial tears before and after mixing were（7.09±0.14）and（7.34±0.33）respectively. Drug release reached 80% at 10 h. Conclusion The eye drops of ion-sensitive in-situ gel loaded with lutein nanoparticles could gelatinize at physiological conditions and increase adhesion to sustain drug release.