头孢呋辛缓释药膜植入兔眼前房的药效学评价

Preliminary evaluation of biodegradable implant for intraocular sustained-release of cefuroxime in rabbits

目的评估植入兔眼前房的可生物降解头孢呋辛缓释药膜的抗感染效用。方法头孢呋辛缓释药膜由头孢呋辛酯(CAE)、高分子聚合物PLGA和聚乙烯吡咯烷酮按一定比例通过溶剂蒸发法制成。50只兔随机分为实验组(n=35):右眼前房植入CAE缓释药膜,对照组(n=15):右眼结膜下注射头孢呋辛125 mg,分别检测对照组注射头孢呋辛后0.5、1、2、6、24 h房水中的药物浓度以及实验组植入CAE药膜后第1、2、3、5、7、14、28天房水和血浆中的药物浓度。实验组植入药膜前后行眼压检测,植入后裂隙灯定期观察前房炎症反应,取角膜组织作扫描电镜和光镜组织学检查,以观察CAE缓释药膜的毒性作用。结果对照组注射头孢呋辛后0.5 h时房水中浓度最高为47 736.18 ng/mL,24 h后浓度极低为10.92 ng/mL;实验组于植入后1周内房水原药浓度>500 ng/mL,第28天时浓度较低为(59.20±39.05)ng/mL,血浆中药物浓度一直处于极低水平(<10 ng/mL)。实验组眼压测量、裂隙灯检查、扫描电镜及组织学检查均无明显异常发现。结论可生物降解头孢呋辛缓释药膜植入兔眼前房后,至少在1周内维持眼内有效药物浓度,而血浆中的药物浓度则极低。兔眼对植入的缓释药膜耐受良好,无明显毒副反应。

Objective To evaluate the anti-infection effects which can be implanted into the anterior chamber in rabbits. of biodegradable implant for sustained release of cefuroxime, Methods The implants for sustained release of cefuroxime were prepared with appropriate mixtures of cefuroxime axetil （CAE） , poly （lactic-glycolic） acid （PLGA） and polyvinyl pyrrolidone by solvent evaporation method. Fifty rabbits were selected and divided into experiment group （ n = 35 ） and control group（n = 15）. The concentrations of cefuroxime in aqueous humor 0.5, 1, 2, 6 and 24 h after subconjunctival injection of 125 mg cefuroxime were measured in control group, and those in aqueous humor and plasma 1, 2, 3, 5, 7, 14 and 28 d after implantation into anterior chamber were detected in experiment group. Besides, for experiment group, the intraocular pressure before and after the implantation were obtained; the inflammation of anterior chamber was routinely observed by slit lamp; and cornea tissues were harvested for scanning electron microscopy and light microscopy. Results The concentration of cefuroxime in aqueous humor in control group reached the highest at 0.5 h after injection of cefuroxime （47 736.18 ng/mL） , while that was extremely low 24 h later （ 10.92 ng/mL）. The concentrations of cefuroxime in aqueous humor were higher than 500 ng/mL within 7 d after implantation, and that was very low at d28 （59.20 ± 39.05 ng/ mL）. And the plasma concentrations of cefuroxime had been at lower levels ever since the implantation（ 〈 10 ng/mL）. No significant abnormal findings were observed by intraocular pressure measurement, slim-lamp microscopy, scanning electron microscopy and histopathological examination. Conclusion The biodegradable implant for sustained release of cefuroxime can maintain effective concentrations in aqueous humor for at least one week with extremely low plasma concentration. The implant is well tolerated in the rabbit eyes with no obvious evidence of toxic effects.