Purchase this article with an account.
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.
Download citation file:
© ARVO (1962-2015); The Authors (2016-present)
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).
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.
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.
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.
This PDF is available to Subscribers Only