title: A poly(ε-caprolactone) device for sustained release of an anti-glaucoma drug.
abstract: Implantable dorzolamide-loaded discs were prepared by blending poly(ε-caprolactone), PCL, with poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide), Lu. By blending, crystallinity, water uptake and mass loss were modified relative to the pure polymers. Burst was diminished by coating the discs with a PCL shell. All samples presented burst release except PCL-coated samples that showed controlled release during 18 days. For PCL-coated samples, barrier control of diffusion coupled with partition control from the core slowed down the release, while for 50/50 Lu/PCL-coated samples, the enhancement in the porosity of the core diminished partition control of drug release. Nonlinear regression analysis suggested that a degradation model fully describes the release curve considering a triphasic release mechanism: the instantaneous diffusion (burst), diffusion and polymer degradation stages. The MTT test indicated that the materials are not cytotoxic for corneal endothelial cells. A good in vitro-in vivo correlation was obtained, with similar amounts of drug released in vitro and in vivo. The discs decreased intraocular pressure (IOP) in normotensive rabbit eyes by 13.0% during 10 days for PCL-coated and by 13.0% during 4 days for 50/50 Lu/PCL-coated samples. The percentages of IOP decrease are similar to those obtained by dorzolamide eyedrop instillation (11.0%).
authors.affiliation: Department of Chemical Engineering, University of Coimbra, Pólo II, Pinhal de Marrocos, 3030-290, Coimbra, Portugal.
authors.forename: Mădălina V
authors.initials: MV
authors.lastname: Natu
authors.forename: Manuel N
authors.initials: MN
authors.lastname: Gaspar
authors.forename: Carlos A Fontes
authors.initials: CA
authors.lastname: Ribeiro
authors.forename: Ilídio J
authors.initials: IJ
authors.lastname: Correia
authors.forename: Daniela
authors.initials: D
authors.lastname: Silva
authors.forename: Hermínio C
authors.initials: HC
authors.lastname: de Sousa
authors.forename: M H
authors.initials: MH
authors.lastname: Gil
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001672:Biocompatible Materials; D002152:Calorimetry, Differential Scanning; D003315:Cornea / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D004058:Diffusion; D016503:Drug Delivery Systems; D005901:Glaucoma / Q000188:drug therapy*; D011091:Polyesters / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry; D016062:Porosity; D011817:Rabbits; D012044:Regression Analysis; D013449:Sulfonamides / Q000008:administration & dosage / Q000737:chemistry*; D013778:Tetrazolium Salts / Q000737:chemistry / Q000494:pharmacology; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology; D013876:Thiophenes / Q000008:administration & dosage / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D000959:Antihypertensive Agents; D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D011091:Polyesters; D011108:Polymers; D013449:Sulfonamides; D013778:Tetrazolium Salts; D013844:Thiazoles; D013876:Thiophenes; C016240:polycaprolactone; C062765:dorzolamide; C022616:thiazolyl blue