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目的地塞米松(dexamethasone,DM)是眼科临床常用药物,但目前缺乏高效、低毒的给药途径。借助生物降解性多聚体材料聚乳酸-羟乙酸(PLGA)构建DM-PLGA纳米粒,兔眼玻璃体内注射可望在眼后节较长时间维持稳定的有效药物浓度。方法乳化/溶剂蒸发法制备载药量分别为20%和50%的DM-PLGA纳米粒,兔眼玻璃体内注射给药后于第1、7、14和21d分别进行临床观察和组织药物浓度的高效液相色谱分析。结果给药后21d内,角膜和房水中药物浓度均低于检测水平下限(10μg·L-1);血浆药物浓度最高为024mg·L-1;载药量20%和50%的2组中视网膜脉络膜药物浓度分别为011-0.42mg·L-1和0.38-0.88mg·L-1,玻璃体药物浓度分别为0.82-26.52mg·L-1和1.78-85.72mg·L-1。临床观察眼底未见异常。结论载药量50%组的DM-PLGA纳米粒在兔眼玻璃体内可维持药物浓度达3周,提示具有眼内注射应用的潜力。
Objective Dexamethasone (DM) is a commonly used ophthalmological drug, but there is no effective and low toxicity route. With the help of biodegradable polymer material PLA-PLGA to construct DM-PLGA nanoparticles, intravitreal injection of rabbit eye is expected to maintain a stable and effective drug concentration for a long time in the posterior eye segment. Methods DM-PLGA nanoparticles with drug loadings of 20% and 50% were prepared by emulsification / solvent evaporation method. The clinical observation and tissue drug concentration of DM-PLGA nanoparticles were carried out on the 1st, 7th, 14th and 21st day after intravitreal injection High Performance Liquid Chromatography. Results Within 21 days after administration, the drug concentration in cornea and aqueous humor was lower than the lower limit of detection (10μg · L-1); the highest plasma concentration was 024mg · L-1; the drug loading was 20% and 50% The retinal choroidal drug concentrations were 011-0.42 mg · L-1 and 0.38-0.88 mg · L-1, respectively, and the vitreous drug concentrations were 0.82-26.52 mg · L-1 and 1.78-85.72 mg · L-1, respectively. Clinical observation of the fundus no abnormalities. Conclusion DM-PLGA nanoparticles with drug loading of 50% could maintain the drug concentration in the vitreous of rabbit eyes for 3 weeks, suggesting the potential of intraocular injection.