科研之友
微信
新浪微博
Facebook
分享链接
摘要
Purpose: Development of a novel formulation for intravitreal administration, in which the endothelin(A) receptor antagonist BQ123 is incorporated in a biodegradable and injectable polymer drug delivery system, poly(2-hydroxyoctanoic acid), aiming at a prolonged retinal vasodilator response. %26lt;br%26gt;Methods: BQ123 was incorporated in poly(2-hydroxyoctanoic acid), leading to an easily injectable, homogenous mixture. In vitro release profiles were obtained in porcine vitreous humor (n = 6). The ex vivo biocompatibility was studied by placing the formulation in contact with porcine retinal tissues and performing histology. In a pilot in vivo study, the change in retinal vessel diameter of mini pigs (n = 2) was followed over 3 h after an intravitreal injection of the formulation, as well as the release of BQ123 from the polymer system for approximately 7 days (n = 6). %26lt;br%26gt;Results: In vitro, a constant release profile was obtained, releasing approximately 91% of BQ123 within 7 days. Histology on the porcine retinal tissues showed good ex vivo biocompatibility. In vivo, a vasodilative response was observed, with a retinal vessel diameter increase from 14% after 15 min, for approximately 39% after 3 h. At t = 3 h, the BQ123 concentration in the vitreous humor was 0.7 +/- 0.2 mu g/mL, followed by 1.5 +/- 1.0 and 1.1 +/- 0.8 mu g/mL after 3 and 7 days, respectively. 39.9%+/- 6.0% of BQ123 was still present in the polymer depot at t = 7 days. %26lt;br%26gt;Conclusions: The results show that an intravitreal injection of this drug delivery system leads to a prolonged vasodilative response and a BQ123 release over 7 days, suggesting its therapeutic potential in the management of retinal ischemic conditions.
- 出版日期2014-8
