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- Title
Development of an Intravitreal Peptide (BQ123) Sustained Release System Based on Poly(2-Hydroxyoctanoic Acid) Aiming at a Retinal Vasodilator Response.
- Authors
Veurink, Marieke; Mangioris, Georgios; Kaufmann, Béatrice; Asmus, Lutz; Hennig, Maren; Heiligenhaus, Arnd; Gurny, Robert; Möller, Michael; Pournaras, Constantin J.
- Abstract
Purpose: Development of a novel formulation for intravitreal administration, in which the endothelinA 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. 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). 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 μg/mL, followed by 1.5±1.0 and 1.1±0.8 μg/mL after 3 and 7 days, respectively. 39.9%±6.0% of BQ123 was still present in the polymer depot at t=7 days. 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.
- Subjects
PEPTIDES; ACIDS; VASODILATORS; ENDOTHELINS; VITREOUS humor; RETINA; INJECTIONS; BIOCOMPATIBILITY
- Publication
Journal of Ocular Pharmacology & Therapeutics, 2014, Vol 30, Issue 6, p517
- ISSN
1080-7683
- Publication type
Article
- DOI
10.1089/jop.2013.0117