Intraocular tissue distribution of betamethasone after intrascleral administration using a non-biodegradable sustained drug delivery device.
OBJECTIVE
To evaluate the tissue distribution of betamethasone (BM) after implantation of a nonbiodegradable intrascleral implant as a new, controlled intraocular delivery system.


METHODS
Nonbiodegradable intrascleral implants designed to release BM for at least 1 month were placed in the sclera of pigmented rabbits. The BM concentrations in the aqueous humor, vitreous, and retina-choroid were determined by high-performance liquid chromatography (HPLC) at 3, 7, 14, and 28 days after implantation. The BM concentrations in three sections of retina-choroid were also investigated. Retinal toxicity was evaluated by electroretinography and histology.


RESULTS
The BM released from the intrascleral implant in vitro and in vivo showed zero-ordered release profiles for 4 weeks. The BM concentrations in the retina-choroid after placement of the intrascleral implants remained higher than effective concentrations for suppressing various inflammatory processes for at least 28 days. The BM concentrations in the retina-choroid around the implantation site were more than 10 times higher than in the opposite side throughout the study. No substantial toxic reactions were observed by electroretinography or histology.


CONCLUSIONS
These findings suggested that the nonbiodegradable intrascleral implant could be a useful drug carrier for intraocular delivery of BM without producing severe retinal toxicity. The intrascleral site may be considered for effective intraocular drug distribution after implantation.
Okabe
Komei
K
Department of Ophthalmology, Nagoya City University Medical School, Nagoya, Japan.
Kimura
Hideya
H
Okabe
Junko
J
Kato
Aki
A
Kunou
Noriyuki
N
Ogura
Yuichiro
Y
D000818:Animals; D001623:Betamethasone / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D001672:Biocompatible Materials; D001673:Biodegradation, Environmental; D002829:Choroid / Q000378:metabolism; D004337:Drug Carriers; D016503:Drug Delivery Systems; D004343:Drug Implants; D005938:Glucocorticoids / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D011145:Polyvinyls; D011817:Rabbits; D012160:Retina / Q000378:metabolism; D012590:Sclera / Q000187:drug effects* / Q000378:metabolism; D014018:Tissue Distribution; D014822:Vitreous Body / Q000378:metabolism
D001672:Biocompatible Materials; D004337:Drug Carriers; D004343:Drug Implants; D005938:Glucocorticoids; D011145:Polyvinyls; C016438:ethylenevinylacetate copolymer; D001623:Betamethasone