Application of clotrimazole via a novel controlled release device provides potent retinal protection.
Age-related macular degeneration is the leading cause of legal blindness among older individuals. Therefore, the development of new therapeutic agents and optimum drug delivery systems for its treatment are crucial. In this study, we investigate whether clotrimazole (CLT) is capable of protecting retinal cells against oxidative-induced injury and the possible inhibitory effect of a sustained CLT-release device against light-induced retinal damage in rats. In vitro results indicated pretreatment of immortalized retinal pigment epithelium cells (RPE-J cells) with 10-50 µM CLT before exposure to oxygen/glucose deprivation conditions for 48 h decreased the extent of cell death, attenuated the percentage of reactive oxygen species-positive cells, and decreased the levels of cleaved caspase-3. The device consists of a separately fabricated reservoir, a CLT formulation, and a controlled release cover, which are made of poly(ethyleneglycol) dimethacrylate (PEGDM) and tri(ethyleneglycol) dimethacrylate (TEGDM). The release rate of CLT was successfully tuned by changing the ratio of PEGDM/TEGDM in the cover. In vivo results showed that use of a CLT-loaded device lessened the reduction of electroretinographic amplitudes after light exposure. These findings indicate that the application of a polymeric CLT-loaded device may be a promising method for the treatment of some retinal disorders.
Division of Clinical Cell Therapy, United Centers for Advanced Research and Translational Medicine (ART), Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, 980-8575, Japan.
Zhaleh Kashkouli
ZK
Nezhad
Nobuhiro
N
Nagai
Kotaro
K
Yamamoto
Hirokazu
H
Kaji
Matsuhiko
M
Nishizawa
Hideyuki
H
Saya
Toru
T
Nakazawa
Toshiaki
T
Abe
D000818:Animals; D002461:Cell Line, Transformed; D003022:Clotrimazole / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D003692:Delayed-Action Preparations; D004343:Drug Implants; D004596:Electroretinography; D008268:Macular Degeneration / Q000188:drug therapy*; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D003692:Delayed-Action Preparations; D004343:Drug Implants; D017382:Reactive Oxygen Species; D003022:Clotrimazole