title: Development of an intravitreal peptide (BQ123) sustained release system based on poly(2-hydroxyoctanoic acid) aiming at a retinal vasodilator response.
abstract: OBJECTIVE
  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.
authors: 1 School of Pharmaceutical Sciences, University of Geneva, University of Lausanne , Geneva, Switzerland .
authors: Marieke
authors: M
authors: Veurink
authors: Georgios
authors: G
authors: Mangioris
authors: Béatrice
authors: B
authors: Kaufmann
authors: Lutz
authors: L
authors: Asmus
authors: Maren
authors: M
authors: Hennig
authors: Arnd
authors: A
authors: Heiligenhaus
authors: Robert
authors: R
authors: Gurny
authors: Michael
authors: M
authors: Möller
authors: Constantin J
authors: CJ
authors: Pournaras
mesh_terms: D000818:Animals; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D016503:Drug Delivery Systems; D065130:Endothelin A Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D058449:Intravitreal Injections; D010456:Peptides, Cyclic / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D010865:Pilot Projects; D011091:Polyesters / Q000737:chemistry*; D012160:Retina / Q000378:metabolism; D012171:Retinal Vessels / Q000187:drug effects* / Q000378:metabolism; D013552:Swine; D013556:Swine, Miniature; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D014822:Vitreous Body / Q000378:metabolism
chemical_list: D003692:Delayed-Action Preparations; D065130:Endothelin A Receptor Antagonists; D010456:Peptides, Cyclic; D011091:Polyesters; D014665:Vasodilator Agents; C570618:poly(2-hydroxyoctanoic acid); C072247:cyclo(Trp-Asp-Pro-Val-Leu)