地塞米松-PLGA纳米粒兔眼玻璃体内注射的药物代谢动力学

Pharmacokinetics characteristics of dexam-ethasone loaded PLGA nanoparticles after in-travitreal injection in rabbits

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 To investigate the release pattern of dexamethasone (DM)loaded PLGA nanoparticles in rabbit eyes. Methods DM-PLGA nanopar-ticles were prepared using a emulsification/solvent evaporation process. After intravitreal injection,DM concentration in various parts of the rabbit eye was measured on day 1,7,14 and 21 by HPLC system. Results Within the experimental duration, nanoparticles containing 50% DM produced drug concentration ranging 0.38-0.88 mg·L-1 in the chorioretina, and 1.78-85.72 mg·L-1 in the vitreous; and that produced by nanoparticles containing 20% DM ranging 0.11-0.42 mg·L-1 in the chorioretina and 0.82-26.52 nig·L-1 in the vitreous, respectively. DM concentration in the cornea and the aqueous humor were both below the limit of detection of the HPLC assay. Clinical observation showed good biocompatibility of the DM-PLGA nanoparticles. Conclusion Nanoparticles containing 50% DM exhibited the effectire dosage maintaining 3 weeks, suggesting great potential for clinical treatment of vitroretinal dis-