May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Sodium Dependent Multi- Vitamin Transporter (SMVT) Targeted Prodrug Approach to Deliver Ganciclovir to Retina
Author Affiliations & Notes
  • D. Kwatra
    Pharmaceutical Sciences, University of Missouri, Kansas City, Missouri
  • K. G. Janoria
    Pharmaceutical Sciences, University of Missouri, Kansas City, Missouri
  • S. H. S. Boddu
    Pharmaceutical Sciences, University of Missouri, Kansas City, Missouri
  • Z. Wang
    Pharmaceutical Sciences, University of Missouri, Kansas City, Missouri
  • A. K. Mitra
    Pharmaceutical Sciences, University of Missouri, Kansas City, Missouri
  • Footnotes
    Commercial Relationships  D. Kwatra, None; K.G. Janoria, None; S.H.S. Boddu, None; Z. Wang, None; A.K. Mitra, None.
  • Footnotes
    Support  NIH RO1 EY09171-12 and RO1 EY10659-10
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 1817. doi:https://doi.org/
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    • Get Citation

      D. Kwatra, K. G. Janoria, S. H. S. Boddu, Z. Wang, A. K. Mitra; Sodium Dependent Multi- Vitamin Transporter (SMVT) Targeted Prodrug Approach to Deliver Ganciclovir to Retina. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1817. doi: https://doi.org/.

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

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Abstract

Purpose: : The objective of this study is to utilize sodium-dependent multiple vitamin transporter (SMVT) system to deliver of ganciclovir (GCV) to the retina using prodrug approach (biotin-GCV).

Methods: : Monoester prodrug of GCV (biotin-GCV) was synthesized in our laboratory by selective protection of one of the two equivalent hydroxyl groups in GCV. In vivo retinal uptake of biotin-GCV was determined in the presence and absence of unconjugated biotin following intravitreal administration. Vitreal disposition of GCV biotin-GCV following administration in rabbit vitreous was studied using microdialysis.

Results: : Retinal uptake of biotin-GCV was significantly inhibited in presence of a specific biotin. Total retinal concentrations GCV were observed in case of biotin-GCV and GCV however total concentration of GCV remaining in the vitreous was found to be more for prodrug in comparison to the parent drug. Significant increase in AUC was found in case of prodrug however rest of the pharmacokinetic parameters such as half life, MRT, Volume of Distribution (Vss) and Cl were found to have no significant difference for both GCV and biotin-GCV.

Conclusions: : Delivery of ganciclovir into the retinal cells can be prolonged utilizing biotin-GCV conjugate. Taken together, the results indicate that biotin-GCV is good alternative to GCV for posterior chamber administration and may lead to enhanced efficacy and decreased frequency of intravitreal administration. Further studies evaluating dose dependency, long-term pharmacokinetic profiles, and in vitro and in vivo efficacy of GCV-biotin against HCMV are needed to fully evaluate the efficacy of this prodrug in CMV retinitis.

Keywords: cytomegalovirus • retina • vitreous 
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