Document Detail


Design and in vitro assessment of L-lactic acid-based copolymers as prodrug and carrier for intravitreal sustained L-lactate release to reverse retinal arteriolar occlusions.
MedLine Citation:
PMID:  23500039     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Ophthalmic conditions in which the retinal vasculature is obstructed generally lead to vision loss. Administration of the vasodilator L-lactate might offer a treatment strategy by restoring the blood flow, but unfortunately its effect after single intravitreal injection is short-lived. This study describes a concept in which the sustained release of L-lactic acid from a biodegradable copolymer system is investigated. The 50:50 (n/n) copolymer system, composed of L-lactic acid and L,D-2-hydroxyoctanoic acid, is a viscous injectable that will form an intravitreal drug depot. Hydrolysis of the copolymer will automatically lead to the release of L-lactic acid, which will convert to L-lactate at physiological pH, thereby providing a carrier and pro-drug in one. In vitro and ex vivo release studies demonstrate an L-lactic acid release over several weeks. Biocompatibility of the co-polymer and its degradation products is shown on a human retinal pigment epithelial cell line and on ex vivo retinal tissues. A low molecular weight copolymer (1200 g/mol) with low polydispersity has promising properties with a zero order release profile, good biocompatibility and injectability.
Authors:
Marieke Veurink; Lutz Asmus; Maren Hennig; Béatrice Kaufmann; Lena Bagnewski; Arnd Heiligenhaus; Efstratios Mendrinos; Constantin J Pournaras; Robert Gurny; Michael Möller
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-3-8
Journal Detail:
Title:  European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences     Volume:  -     ISSN:  1879-0720     ISO Abbreviation:  Eur J Pharm Sci     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-3-18     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9317982     Medline TA:  Eur J Pharm Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013. Published by Elsevier B.V.
Affiliation:
School of Pharmaceutical Sciences, University of Geneva, University of Lausanne, 1211, Geneva, Switzerland.
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