Feasibility of drug delivery to the posterior pole of the rabbit eye with an episcleral implant.
OBJECTIVE
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.
Kato
Aki
A
Department of Ophthalmology, Nagoya City University Medical School, Nagoya, Japan.
Kimura
Hideya
H
Okabe
Komei
K
Okabe
Junko
J
Kunou
Noriyuki
N
Ogura
Yuichiro
Y
D000818:Animals; D001082:Aqueous Humor / Q000187:drug effects / Q000378:metabolism; D001623:Betamethasone / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D001672:Biocompatible Materials; D001682:Biological Availability; D002829:Choroid / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D016503:Drug Delivery Systems; D004343:Drug Implants; D004596:Electroretinography; D005240:Feasibility Studies; D005452:Fluoresceins; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D008856:Microscopy, Fluorescence; D011817:Rabbits; D012160:Retina / Q000187:drug effects / Q000378:metabolism; D012590:Sclera / Q000187:drug effects* / Q000378:metabolism; D014822:Vitreous Body / Q000187:drug effects / Q000378:metabolism
D001672:Biocompatible Materials; D004343:Drug Implants; D005452:Fluoresceins; D005938:Glucocorticoids; C093616:6-carboxyfluorescein diacetate; D001623:Betamethasone