May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Episcleral Polymeric Devices for Localized Topotecan Chemotherapy: Implications in Retinoblastoma Treatment
Author Affiliations & Notes
  • A. M. Carcaboso
    Univ de Buenos Aires, Buenos Aires, Argentina
    Pharmacology, Ophthalmology,
  • D. A. Chiappetta
    Univ de Buenos Aires, Buenos Aires, Argentina
    Pharmaceutical Technology, Hemato-Oncology,
  • A. Sosnik
    Univ de Buenos Aires, Buenos Aires, Argentina
    Pharmaceutical Technology, Hemato-Oncology,
  • J. A. W. Opezzo
    Univ de Buenos Aires, Buenos Aires, Argentina
    Pharmacology, Ophthalmology,
  • A. C. Fandino
    Pharmacology, Ophthalmology,
    Hospital J.P. Garrahan, Buenos Aires, Argentina
  • C. Hocht
    Univ de Buenos Aires, Buenos Aires, Argentina
    Pharmacology, Ophthalmology,
  • J. O. Croxatto
    Fundacion Oftalmologica Argentina J Malbran, Buenos Aires, Argentina
  • G. F. Bramuglia
    Univ de Buenos Aires, Buenos Aires, Argentina
    Pharmacology, Ophthalmology,
  • D. H. Abramson
    Ophthalmic Oncology Service, Memorial Sloan-Ketering Cancer Center, NY, New York
  • G. L. Chantada
    Pharmaceutical Technology, Hemato-Oncology,
    Hospital J.P. Garrahan, Buenos Aires, Argentina
  • Footnotes
    Commercial Relationships  A.M. Carcaboso, None; D.A. Chiappetta, None; A. Sosnik, None; J.A.W. Opezzo, None; A.C. Fandino, None; C. Hocht, None; J.O. Croxatto, None; G.F. Bramuglia, None; D.H. Abramson, None; G.L. Chantada, None.
  • Footnotes
    Support  Fund for Ophthalmic Knowledge (GLC, ACF, AMC); MEC Grant EX2005-0201(AMC)
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 3180. doi:https://doi.org/
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      A. M. Carcaboso, D. A. Chiappetta, A. Sosnik, J. A. W. Opezzo, A. C. Fandino, C. Hocht, J. O. Croxatto, G. F. Bramuglia, D. H. Abramson, G. L. Chantada; Episcleral Polymeric Devices for Localized Topotecan Chemotherapy: Implications in Retinoblastoma Treatment. Invest. Ophthalmol. Vis. Sci. 2008;49(13):3180. doi: https://doi.org/.

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

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Abstract

Purpose: : To develop an alternative treatment for retinoblastoma based on the use of episcleral devices made of biocompatible polymers, allowing for a more selective, controlled and sustained release of topotecan to the posterior segment of the eye.

Methods: : We developed polycaprolactone devices loaded with 2 mg topotecan and their release profile was assessed in vitro. The devices were surgically inserted subconjunctivally in two groups of non tumor bearing albino rabbits (n=5-8 rabbits per group) and their ocular and systemic pharmacokinetic features were assessed in vivo. One of the groups received a local vacoconstrictor (adrenaline) loaded together with topotecan into the device.

Results: : In vitro, a biphasic release profile was observed in the developed devices. In vivo, using our topotecan-loaded implants we were able to achieve a more selective and prolonged delivery of the drug to the vitreous, and high concentrations at tissues in contact with the implant (sclera, choroid and retina). Clinically relevant concentrations of topotecan in the vitreous were detectable (10 ng/mL) and sustained for at least 24 hours. Local vasoconstriction significantly improved the trans-scleral delivery of topotecan. Systemic exposure to the drug was minimal in both groups of rabbits.

Conclusions: : By using episcleral devices and local vasoconstriction, topotecan can be selectively delivered to the treated eye. The relevance of this strategy as a treatment for retinoblastoma should be tested in clinical studies.

Keywords: retinoblastoma • oncology • vitreous 
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