May 2007
Volume 48, Issue 13
ARVO Annual Meeting Abstract  |   May 2007
Topotecan Periocular Delivery for Retinoblastoma Chemotherapy
Author Affiliations & Notes
  • A. M. Carcaboso
    Universidad de Buenos Aires, Buenos Aires, Argentina
  • G. L. Chantada
    Hospital J.P. Garrahan, Buenos Aires, Argentina
  • G. F. Bramuglia
    Universidad de Buenos Aires, Buenos Aires, Argentina
  • A. C. Fandino
    Hospital J.P. Garrahan, Buenos Aires, Argentina
  • D. A. Chiappetta
    Universidad de Buenos Aires, Buenos Aires, Argentina
    Pharmaceutical Technology,
  • D. H. Abramson
    Ophthalmic Oncology Service, Memorial Sloan-Ketering Cancer Center, NY, New York
  • Footnotes
    Commercial Relationships A.M. Carcaboso, None; G.L. Chantada, None; G.F. Bramuglia, None; A.C. Fandino, None; D.A. Chiappetta, None; D.H. Abramson, None.
  • Footnotes
    Support Fund for Ophthalmic Knowledge; MEC Grant EX2005-0201; UBACYT B025
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 5260. doi:
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    • Get Citation

      A. M. Carcaboso, G. L. Chantada, G. F. Bramuglia, A. C. Fandino, D. A. Chiappetta, D. H. Abramson; Topotecan Periocular Delivery for Retinoblastoma Chemotherapy. Invest. Ophthalmol. Vis. Sci. 2007;48(13):5260.

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      © ARVO (1962-2015); The Authors (2016-present)

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To study topotecan (TPT) access to the vitreous when administeredby periocular injection (p.o.i.) as compared to intravenous(i.v.) infusion. To design biodegradable implants suitable fortransscleral delivery of TPT for retinoblastoma chemotherapy.


21 rabbits received 1 mg TPT by p.o.i. and 14 rabbits by i.v.infusion. TPT-loaded polycaprolactone implants (0.25 mg TPTin 120 mg total weight), coated in the side not facing the sclera,were obtained by a melt-molding method.


The figure displays vitreous levels of total (triangles) andactive 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 indicatedby 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).Thesystemic absorption from the periocular depot led to high TPTplasma exposures (AUCp.o. = 339 ± 10; AUCi.v. = 338 ±10 ng×h/mL).Implants (D) released near 100 % TPT in vitro in7 days (E). Most interestingly, the rapid hydrolysis of TPTto inactive carboxylate at pH 7.4 was avoided and the activelactone form was preferentially released throughout the study. 


Our results show that after periocular injection of TPT systemicabsorption accounts for most of its vitreous delivery. The needfor a preferentially transscleral delivery was evidenced anda candidate system was designed. 

Keywords: retinoblastoma • vitreous 

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