OCULAR-SELECTIVE TOPOTECAN DELIVERY BY EPISCLERAL POLYMERIC IMPLANTS FOR ALTERNATIVE RETINOBLASTOMA TREATMENT

CARCABOSO A.M.; BRAMUGLIA G.F.; CHIAPPETTA D.A.; OPEZZO J.A.W.; FANDIÑO A.C.; DE DAVILA M.T.G.; HOCHT C.; RUBIO M.C.; ABRAMSON D.H.; CHANTADA G.L.

SIENA, ITALIA

Congreso; ISSO MEETING 2007; 2007

INTERNATIONAL SOCIETY OF OCULAR ONCOLOGY

Although systemic chemotherapy has become the initial treatment for intraocular retinoblastoma worldwide, significant complications including fatal secondary leukemia have been reported. Intravenous topotecan is a promising agent for treatment of intraocular retinoblastoma because it penetrates to the eye but is also potentially toxic, so we have developed a novel delivery system using episcleral (biocompatible) systems. Polymeric topotecan-loaded devices were manufactured, characterized and surgically implanted subconjunctivally in 9 albino rabbits (Implant Group). A group of 6 rabbits received topotecan intravenous injection (IV Group). A microdialysis probe was customized and inserted in the vitreous chamber for continuous sampling. Topotecan loaded implants released high topotecan amounts initially and sustained levels later, following a rationale approach for tumor chemotherapy. Statistically significant differences were observed between topotecan levels detected in treated and contralateral eyes of the Implant Group (during the first hours post-implantation P<0.01) and lower levels after the second day. Topotecan lactone levels were below detection limits as compared to the high levels reached in the IV Group. Insummary, we developed an ocular-selective delivery of topotecan by a polymeric episcleral device.