PMID- 14691179 OWN - NLM STAT- MEDLINE DCOM- 20040120 LR - 20190607 IS - 0146-0404 (Print) IS - 0146-0404 (Linking) VI - 45 IP - 1 DP - 2004 Jan TI - Feasibility of drug delivery to the posterior pole of the rabbit eye with an episcleral implant. PG - 238-44 AB - PURPOSE: To evaluate the feasibility of a nonbiodegradable polymeric episcleral implant as a new controlled intraocular delivery system of betamethasone (BM) to the posterior pole of the eye. METHODS: The episcleral implant, which is composed of a drug-releasing component and a suture tag, released BM through an ethylene vinyl acetate membrane. The implants were placed on the sclera in 12 eyes of 12 Japanese white rabbits so that the drug-releasing surface could attach to the sclera at the posterior pole. BM concentrations in the aqueous humor, vitreous, and retina-choroid (posterior half and anterior half) were determined by high-performance liquid chromatography (HPLC) at weeks 1, 2, and 4 after implantation. In addition, the intraocular tissue distribution of the drug was evaluated by fluorescein microscopy after implantation of the implant loaded with 6-carboxy fluorescein diacetate (6-CFDA) as a drug marker. Retinal toxicity was evaluated by electroretinography and histologic examination. RESULTS: The implant showed zero-order release profiles both in vitro and in vivo for 4 weeks. BM concentrations in the retina-choroid after implantation were maintained above the concentrations effective for suppressing inflammatory reactions for at least 4 weeks. The BM concentration was greater in the posterior half of the retina-choroid than in the vitreous. It was confirmed that 6-CFDA penetrated through the sclera and dispersed into the retina-choroid. Fluorescence from 6-CFDA gradually decreased in intensity with increased distance from the implantation site. Electroretinography and histologic study showed no substantial toxic reactions. CONCLUSIONS: These findings suggest that the episcleral implant may be a useful drug carrier for intraocular delivery of BM, especially for the posterior part of the eye. FAU - Kato, Aki AU - Kato A AD - Department of Ophthalmology, Nagoya City University Medical School, Nagoya, Japan. FAU - Kimura, Hideya AU - Kimura H FAU - Okabe, Komei AU - Okabe K FAU - Okabe, Junko AU - Okabe J FAU - Kunou, Noriyuki AU - Kunou N FAU - Ogura, Yuichiro AU - Ogura Y LA - eng PT - Journal Article PL - United States TA - Invest Ophthalmol Vis Sci JT - Investigative ophthalmology & visual science JID - 7703701 RN - 0 (Biocompatible Materials) RN - 0 (Drug Implants) RN - 0 (Fluoresceins) RN - 0 (Glucocorticoids) RN - 3348-03-6 (6-carboxyfluorescein diacetate) RN - 9842X06Q6M (Betamethasone) SB - IM MH - Animals MH - Aqueous Humor/drug effects/metabolism MH - Betamethasone/*administration & dosage/pharmacokinetics/toxicity MH - Biocompatible Materials MH - Biological Availability MH - Choroid/drug effects/metabolism MH - Chromatography, High Pressure Liquid MH - *Drug Delivery Systems MH - Drug Implants MH - Electroretinography MH - Feasibility Studies MH - Fluoresceins MH - Glucocorticoids/*administration & dosage/pharmacokinetics/toxicity MH - Microscopy, Fluorescence MH - Rabbits MH - Retina/drug effects/metabolism MH - Sclera/*drug effects/metabolism MH - Vitreous Body/drug effects/metabolism EDAT- 2003/12/24 05:00 MHDA- 2004/01/21 05:00 CRDT- 2003/12/24 05:00 PHST- 2003/12/24 05:00 [pubmed] PHST- 2004/01/21 05:00 [medline] PHST- 2003/12/24 05:00 [entrez] AID - 10.1167/iovs.02-1258 [doi] PST - ppublish SO - Invest Ophthalmol Vis Sci. 2004 Jan;45(1):238-44. doi: 10.1167/iovs.02-1258.