TOPOTECAN PERIOCULAR DELIVERY FOR RETINOBLASTOMA CHEMOTHERAPY

CARCABOSO A.M.; CHANTADA G.L.; BRAMUGLIA G.F.; FANDIÑO A.C.; CHIAPPETTA D.A.; ABRAMSON D.H.

FORT LAUDERDALE, FLORIDA, USA

Congreso; THE AGING EYE ARVO ANNUAL MEETING 2007; 2007

ASSOCIATION FOR RESEARCH IN VISION AND OPHTHALMOLOGY

Purpose: To study topotecan (TPT) access to the vitreous when administered by periocular injection (p.o.i.) as compared to intravenous (i.v.) infusion. To design biodegradable implants suitable for transscleral delivery of TPT for retinoblastoma chemotherapy.Methods: 21 rabbits received 1 mg TPT by p.o.i. and 14 rabbits by i.v. infusion. TPT-loaded polycaprolactone implants (0.25 mg TPT in 120 mg total weight), coated in the side not facing the sclera, were obtained by a melt-molding method.Results: The figure displays vitreous levels of total (triangles) and active lactone (circles) TPT in treated (A) and contralateral (B) eyes after p.o.i. administration and after i.v. infusion (C). Similar vitreous lactone exposures were found, as indicated by the area under the curve (AUCtreated p.o. = 34.0 ± 3.9; AUCcontrol p.o. = 35.3 ± 4.0; AUCi.v. = 36.4 ± 4.1 ng×h/mL). The systemic absorption from the periocular depot led to high TPT plasma exposures (AUCp.o. = 339 ± 10; AUCi.v. = 338 ± 10 ng×h/mL). Implants (D) released near 100 % TPT in vitro in 7 days (E). Most interestingly, the rapid hydrolysis of TPT to inactive carboxylate at pH 7.4 was avoided and the active lactone form was preferentially released throughout the study.Conclusions: Our results show that after periocular injection of TPT systemic absorption accounts for most of its vitreous delivery. The need for a preferentially transscleral delivery was evidenced and a candidate system was designed.