Sustained release of ganciclovir and foscarnet from biodegradable scleral plugs for the treatment of cytomegalovirus retinitis.
The purpose of this report was to develop solvent-free biodegradable scleral plugs for simultaneous ganciclovir and foscarnet delivery for cytomegalovirus retinitis treatment. To fabricate a biodegradable plug, polylactide-polyglycolide copolymers were pre-mixed with the drugs. The mixture was then compression molded and sintered to form a compact scleral plug. The drug release features were monitored with HPLC assay both in vitro and in vivo. Both drugs showed a biphasic release curvature with an initial burst and followed by a second sustained release phase and maintained at therapeutic level for 3-4 weeks. As compared to ganciclovir, foscarnet was released faster in initial phase, but later, showed extended retention in vitreous humor. For biocompatibility analysis, dark-adapted flash electroretinography was performed, and the a-wave and b-wave amplitudes were statistically equal before and after the scleral plug implantation. Finally, serial microstructure changes of releasing scleral plugs were evaluated with scanning electron microscope. The scleral plug surface showed progressive transformation from granular solid surface to smoothen and cavitated appearance.
Peng
Yi-Jie
YJ
Department of Ophthalmology, Buddhist Tzu Chi General Hospital-Taipei Branch, Taipei, Taiwan, ROC.
Wen
Chin-Wei
CW
Chiou
Shih-Hwa
SH
Liu
Shih-Jung
SJ
D000818:Animals; D001672:Biocompatible Materials / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D003228:Conjunctiva / Q000473:pathology; D017726:Cytomegalovirus Retinitis / Q000188:drug therapy* / Q000473:pathology; D003623:Dark Adaptation; D003692:Delayed-Action Preparations; D004596:Electroretinography; D017245:Foscarnet / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015774:Ganciclovir / Q000493:pharmacokinetics / Q000627:therapeutic use*; D019919:Prosthesis Implantation; D011817:Rabbits; D012590:Sclera / Q000473:pathology* / Q000648:ultrastructure; D012599:Sclerostomy
D001672:Biocompatible Materials; D003692:Delayed-Action Preparations; D017245:Foscarnet; D015774:Ganciclovir