title: Controlled release of ethacrynic acid from poly(lactide-co-glycolide) films for glaucoma treatment.
abstract: Ethacrynic acid (ECA) is a potential glaucoma drug that can reduce intraocular pressure. However, conventional methods of ECA administration may cause toxicity to normal eye tissues and are inconvenient to patients. Therefore, we developed and characterized an ECA loaded poly(lactide-co-glycolide) (PLGA) copolymer film, and quantified the therapeutic efficacy of the film implanted in the rabbit eye. In the aqueous medium, the release of ECA from the PLGA50:50 film was time dependent and more than 90% of ECA was released within a week. This release profile was consistent with the kinetics of water uptake and microstructural changes of PLGA50:50 films as revealed by an electron microscopy examination. ECA release and PLGA degradation caused a gradual pH decrease in the release medium. The total pH decrease was 0.4 unit in 3 days. We also observed that the initial rate of ECA release was positively correlated with the weight ratio of ECA versus PLGA and inversely correlated with the molar ratio of lactide versus glycolide in PLGA films. At the end of a 3-day incubation, the cumulative release of ECA from PLGA50:50, PLGA85:15 and PLGA100:00 films were 78.8%, 9.35% and 3.60%, respectively. When the PLGA50:50 film loaded with ECA was implanted into the sclera of rabbit eyes, the intraocular pressure was significantly reduced and the reduction was maintained for at least 10 days. These data indicate that PLGA films have a potential to be used as a controlled ECA release device for glaucoma treatment.
authors.affiliation: Department of Biomedical Engineering, Duke University, Box 90281, Durham, NC 27708, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Wang
authors.forename: Pratap
authors.initials: P
authors.lastname: Challa
authors.forename: David L
authors.initials: DL
authors.lastname: Epstein
authors.forename: Fan
authors.initials: F
authors.lastname: Yuan
mesh_terms: D000042:Absorption; D000818:Animals; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry*; D004058:Diffusion; D004353:Drug Evaluation, Preclinical; D004976:Ethacrynic Acid / Q000008:administration & dosage* / Q000737:chemistry*; D005901:Glaucoma / Q000188:drug therapy*; D007429:Intraocular Pressure / Q000187:drug effects*; D019344:Lactic Acid / Q000737:chemistry*; D008567:Membranes, Artificial; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry*; D016062:Porosity; D011817:Rabbits; D013499:Surface Properties; D016896:Treatment Outcome; D014867:Water / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D008567:Membranes, Artificial; D011108:Polymers; D014867:Water; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004976:Ethacrynic Acid