Sustained release of ganciclovir and foscarnet from biodegradable scleral plugs for the treatment of cytomegalovirus retinitis

Abstract 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...

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Bibliographic Details
Published in:Biomaterials 2010-03, Vol.31 (7), p.1773-1779
Main Authors: Peng, Yi-Jie, Wen, Chin-Wei, Chiou, Shih-Hwa, Liu, Shih-Jung
Format: Article
Language:English
Subjects:
Advanced Basic Science
Animals
Biocompatible Materials - pharmacokinetics
Biocompatible Materials - therapeutic use
Biodegradable scleral plugs
Chromatography, High Pressure Liquid
Conjunctiva - pathology
Cytomegalovirus
Cytomegalovirus retinitis
Cytomegalovirus Retinitis - drug therapy
Cytomegalovirus Retinitis - pathology
Dark Adaptation
Delayed-Action Preparations
Dentistry
Electroretinography
Foscarnet
Foscarnet - pharmacokinetics
Foscarnet - therapeutic use
Ganciclovir
Ganciclovir - pharmacokinetics
Ganciclovir - therapeutic use
Intravitreal sustained release
Polylactide–polyglycolide
Prosthesis Implantation
Rabbits
Sclera - pathology
Sclera - ultrastructure
Sclerostomy
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Summary:Abstract 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.
ISSN:0142-9612
1878-5905
DOI:10.1016/j.biomaterials.2009.11.039