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目的制备一种聚乙二醇修饰的壳聚糖纳米粒,评价其局部滴眼给药性能。方法以伏立康唑为模型药物,采用离子交联法制备载药的聚乙二醇化壳聚糖纳米粒,对其进行表征后,分别考察纳米粒的药物缓释能力、对眼表药物代谢动力学的影响及其角膜渗透性。结果聚乙二醇化壳聚糖纳米粒粒径为(235±23)nm,Zeta电位为(+23.1±0.6)mV,载药量为11.16%,包封率为61.35%。纳米粒体外释放药物非常缓慢,可持续释药48 h;相比于伏立康唑水溶液,纳米粒的药物浓度-时间曲线下面积明显增加,药物半衰期延长,清除率减少,眼表药物平均滞留时间延长(P<0.05)。荧光标记的聚乙二醇化壳聚糖纳米粒可穿透角膜上皮逐渐向角膜基质渗透。结论与药物水溶液相比,聚乙二醇化壳聚糖纳米粒能够有效减少眼表药物的流失,改善药物的生物利用度。
Objective To prepare a polyethylene glycol modified chitosan nanoparticles for evaluation of local eye drops. Methods Voriconazole was used as a model drug to prepare drug-loaded PEGylated chitosan nanoparticles by ion-crosslinking method. The drug-releasing properties of nanoparticles were investigated respectively. The pharmacokinetics Effect and its corneal permeability. Results The particle size of PEGylated chitosan nanoparticles was (235 ± 23) nm and the Zeta potential was (+23.1 ± 0.6) mV. The drug loading was 11.16% and the entrapment efficiency was 61.35%. Compared with voriconazole aqueous solution, the area under the drug concentration-time curve of nanoparticles significantly increased, the half-life of drugs was extended, the clearance rate was reduced, and the average retention time of ocular surface drugs was prolonged P <0.05). Fluorescently labeled PEGylated chitosan nanoparticles penetrate the corneal epithelium gradually into the corneal stroma. Conclusion PEGylated chitosan nanoparticles can effectively reduce the loss of ocular surface drug and improve the bioavailability of drug compared with aqueous solution.