ABSTRACT
Delivering effective drugs at sufficiently high concentrations to the area of infection is a standard treatment for infectious disease, such as endophthalmitis. This is currently done by empirical trans pars plana intravitreal injection of both antibiotics directed against gram-positive and gram-negative microorganisms and steroids. However, injections by needles repeatedly may increase the risks of intraocular infection and hemorrhage, as well as retinal detachment. This article explores the alternative of using biodegradable polymers as scleral plugs for a long-term drug release in vivo. To manufacture plugs, poly(lactide-glycolide) copolymers were first mixed with vancomycin, amikacin, and dexamethasone. The mixture was compressed and sintered at 55 degrees C to form scleral plugs 1.4 mm in diameter. Biodegradable scleral plugs released high concentrations of antibiotics (well above the minimum inhibitory concentrations, MIC) and steroids in vivo for the period of time needed to treat intraocular infection. In addition, no major complications such as infectious or sterile endophthalmitis, retinal detachment, ocular phthisis, or uvea protrusion at sclerotomy site were observed throughout the experiment. The sclerotomy wound healed after total degradation of the scleral implants without leakage or local necrosis. Antibiotic/steroid-impregnated biodegradable scleral plugs may have a potential role in the treatment of various intraocular infections.
Subject(s)
Amikacin/administration & dosage , Anti-Bacterial Agents/administration & dosage , Anti-Inflammatory Agents/administration & dosage , Dexamethasone/administration & dosage , Drug Delivery Systems , Sclera/surgery , Vancomycin/administration & dosage , Amikacin/pharmacokinetics , Amikacin/pharmacology , Amikacin/therapeutic use , Animals , Anti-Bacterial Agents/pharmacokinetics , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Anti-Inflammatory Agents/pharmacokinetics , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Biocompatible Materials/chemistry , Biocompatible Materials/metabolism , Dexamethasone/pharmacokinetics , Dexamethasone/pharmacology , Dexamethasone/therapeutic use , Drug Carriers/chemistry , Drug Carriers/metabolism , Endophthalmitis/drug therapy , Lactic Acid/chemistry , Lactic Acid/metabolism , Materials Testing , Polyglycolic Acid/chemistry , Polyglycolic Acid/metabolism , Polylactic Acid-Polyglycolic Acid Copolymer , Prostheses and Implants , Rabbits , Sclera/anatomy & histology , Sclera/drug effects , Sclera/pathology , Solvents , Vancomycin/pharmacokinetics , Vancomycin/pharmacology , Vancomycin/therapeutic useABSTRACT
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.
