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Pharmacokinetics of HM-3 after intravitreal administration in mice eye           ★★★
Pharmacokinetics of HM-3 after intravitreal administration in mice eye
作者:袁冬青 文章来源:南京医科大学第一附属医院 点击数:213 更新时间:2012/9/13
Purpose: HM-3, an RGD modified endostatin-derived polypeptide, is a potent angiogenesis inhibitor synthesized in our laboratory, The robust inhibitory effects of HM-3 on endothelial cell migration and tumour growth have been demonstrated by in vivo and in vitro activity assays. This study investigated the pharmacokinetics of intravitreally administered in mice eyes.

Methods: HM-3 (1 μl, 20mg/ml) was instilled into the mice’s intravitrouse. The mice were sacrificed at 3, 6, 12, 24, 48, 72, 96, 120, 144, and 168 hour after the administration and ocular tissues were obtained. The concentrations of HM-3 inchorioidea, retina and serum were determined by indirect competitive ELISA.

Results: After intravitreal administration, there was wide distribution and different clearance of HM-3 among the various ocular tissues. The mean maximum choroidal concentration of HM-3 (1772.595 ng/ml) was measured at 48 hour, and maximum retinal concentrations of HM-3 (1411.262 ng/ml) was measured at 72 hour. Serum HM-3 concentration peaked at 144 hour (4181.444 ng/ml). The mean half-life values in chorioidea, retina and serum were 97.58, 103.24, and 120.88 hours, respectively. Concentration of HM-3 inthe chorioidea of the noninjected eye peaked at 96 hour (0.135 ng/ml) and declined to 0.038 ng/ml at 168 hour. In the retina and serum of the noninjected eye, the mean maximum concentration of HM-3 was achieved at 120 hour (0.213 ng/ml) and 96 hour (0.404 ng/ml), and declined to 0.110 ng/ml in retina and 0.168 ng/ml in serum at 168 hour, respectively.

Conclusions: Measurable concentrations of HM-3 are achieved in ocular tissues after intravitrouse application in mice model. Carrying out the research into pharmacokinetics of HM-3 provides the information for laying down drug delivery scheme in mice model of choroidal neovascularization.
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