Etoposide-Loaded Poly(Lactic-co-Glycolic Acid) Intravitreal Implants: In Vitro and In Vivo Evaluation

Ana Gabriela Reis Solano, Adriana de Fátima Pereira, Luiz Gustavo Amorim de Faria, Silvia Ligório Fialho, Patrícia Santiago de Oliveira Patricio, Armando da Silva-Cunha, Gustavo Oliveira Fulgêncio, Gisele Rodrigues da Silva, Gérson Antônio Pianetti

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.