ABSTRACT
Etoposide-loaded poly(lactic-co-glycolic acid) implants were developed for intravitreal application. Implants were prepared by a solvent-casting method and characterized in terms of content uniformity, morphology, drug-polymer interaction, stability, and sterility. In vitro drug release was investigated and the implant degradation was monitored by the percent of mass loss. Implants were inserted into the vitreous cavity of rabbits' eye and the in vivo etoposide release profile was determined. Clinical examination and the Hen Egg Test-Chorioallantoic Membrane (HET-CAM) method were performed to evaluate the implant tolerance. The original chemical structure of the etoposide was preserved after incorporation in the polymeric matrix, which the drug was dispersed uniformly. In vitro, implants promoted sustained release of the drug and approximately 57% of the etoposide was released in 50 days. In vivo, devices released approximately 63% of the loaded drug in 42 days. Ophthalmic examination and HET-CAM assay revealed no evidence of toxic effects of implants. These results tend to show that etoposide-loaded implants could be potentially useful as an intraocular etoposide delivery system in the future.
Subject(s)
Drug Implants/metabolism , Etoposide/metabolism , Lactic Acid/metabolism , Polyglycolic Acid/metabolism , Vitreous Body/metabolism , Animals , Chickens , Drug Implants/administration & dosage , Drug Implants/chemistry , Etoposide/administration & dosage , Etoposide/chemistry , Intravitreal Injections , Lactic Acid/administration & dosage , Lactic Acid/chemistry , Male , Polyglycolic Acid/administration & dosage , Polyglycolic Acid/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer , Rabbits , Vitreous Body/drug effectsABSTRACT
In this study, the effects of the controlled and sustained release of methotrexate from poly(É-caprolactone) implants were evaluated in the solid Ehrlich tumor. The drug locally leached from the implantable devices was capable of reducing the tumor growth and the necrotic areas of the tumor site. Furthermore, the methotrexate exerted its anti-tumor effect probably by the recruitment of neutrophils at the tumor site, which assisted in modulating the growth of the tumor. The polymeric implants containing methotrexate could be a chemotherapic alternative to treat locally solid tumors with lower systemic side effects.
Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Carcinoma, Ehrlich Tumor/drug therapy , Drug Carriers/chemistry , Methotrexate/therapeutic use , Polyesters/chemistry , Animals , Antimetabolites, Antineoplastic/administration & dosage , Antimetabolites, Antineoplastic/adverse effects , Body Weight/drug effects , Carcinoma, Ehrlich Tumor/metabolism , Carcinoma, Ehrlich Tumor/pathology , Cell Proliferation/drug effects , Drug Carriers/administration & dosage , Drug Carriers/adverse effects , Drug Implants , Female , Immunohistochemistry , Methotrexate/administration & dosage , Methotrexate/adverse effects , Mice , Polyesters/administration & dosage , Polyesters/adverse effectsABSTRACT
Poly(ε-caprolactone) implants containing etoposide, an important chemotherapeutic agent and topoisomerase II inhibitor, were fabricated by a melt method and characterized in terms of content uniformity, morphology, drug physical state, and sterility. In vitro and in vivo drug release from the implants was also evaluated. The cytotoxic activity of implants against HeLa cells was studied. The short-term tolerance of the implants was investigated after subcutaneous implantation in mice. The original chemical structure of etoposide was preserved after incorporation into the polymeric matrix, in which the drug was dispersed uniformly. Etoposide was present in crystalline form in the polymeric implant. In vitro release study showed prolonged and controlled release of etoposide, which showed cytotoxicity activity against HeLa cells. After implantation, good correlation between in vitro and in vivo drug release was found. The implants demonstrated good short-term tolerance in mice. These results tend to show that etoposide-loaded implants could be potentially applied as a local etoposide delivery system.
