Biodegradable scleral implant for intravitreal controlled release of ganciclovir.
BACKGROUND
The aims of this study were to develop biodegradable scleral implants that could overcome previously reported disadvantages such as an adverse burst in the late phase of release and to investigate the release profile of modified scleral implants in vitro and in vivo.


METHODS
The modified scleral implants (weight 8.5 mg, length 5 mm) were made of mixtures of poly(DL-lactide) (PLA) with different molecular weights and contained 25 weight % of ganciclovir (GCV). The release of GCV was evaluated in vitro by spectrophotometry. Intravitreal GCV concentrations in vivo were measured by high-performance liquid chromatography following plug implantation in pigmented rabbits. The biocompatibility of the device was determined by indirect ophthalmoscopy and light microscopy.


RESULTS
The in vitro release studies showed stable, long-term sustained and slow release. The in vivo release studies showed that the implants had long-term release in the diffusional phase of the triphasic release pattern and only a minor adverse burst of GCV in the late phase. No significant retinal toxicity was observed by histologic examination.


CONCLUSIONS
Our findings showed that this newly modified scleral implant may provide suitable intravitreal drug delivery for treatment of cytomegalovirus retinitis.
Yasukawa
T
T
Department of Ophthalmology and Visual Sciences, Graduate School of Medicine, Kyoto University, Japan.
Kimura
H
H
Kunou
N
N
Miyamoto
H
H
Honda
Y
Y
Ogura
Y
Y
Ikada
Y
Y
D020341:Absorbable Implants; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001672:Biocompatible Materials; D002851:Chromatography, High Pressure Liquid; D004343:Drug Implants; D015828:Eye Infections, Viral / Q000188:drug therapy; D015774:Ganciclovir / Q000008:administration & dosage* / Q000493:pharmacokinetics; D011091:Polyesters; D011817:Rabbits; D012160:Retina / Q000166:cytology / Q000187:drug effects; D012590:Sclera / Q000601:surgery*; D013053:Spectrophotometry; D014822:Vitreous Body / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D000998:Antiviral Agents; D001672:Biocompatible Materials; D004343:Drug Implants; D011091:Polyesters; C033616:poly(lactide); D015774:Ganciclovir