Ganciclovir Release Rates in Vitreous from Different Formulations of 1-O-Hexadecylpropanediol-3-Phospho-Ganciclovir

Abstract

In vitreous, HDP-P-GCV as a crystalline formulation was converted to GCV more rapidly than liposomal formulation of HDP-P-GCV. Vitreous cells may play an important role in the metabolism of either formulation of HDP-P-GCV delivered into vitreous.

Characterization of a Novel Intraocular Drug-Delivery System Using Crystalline Lipid Antiviral Prodrugs of Ganciclovir and Cyclic Cidofovir

“…The dissolved molecules enter the cells and are cleaved intracellularly by phospholipase C into hexadecyloxypropanol and the parent drug. 9 In the present study, we used the same concept and technique to synthesize an ether lipid ester of cyclic cidofovir, HDP-cCDV. Intravitreal injection of 100 g or lower doses of HDP-cCDV crystals provided an ideal drug depot that floated in the inferior vitreous cavity without disturbing the visual axis.…”

“…There was little parent drug detectable when prodrug was incubated with a heatinactivated vitreous sample, but conversion was detected readily by native vitreous that contains cells. 9 It has been known that CDV is phosphorylated to cidofovir diphosphate, the active form of cidofovir that has a long intracellular halflife. 13 Indeed, the pretreatment studies indicated at least 100 days of pharmacologic effect against HSV-1 infection of the rabbit retina.…”

Micelle formulation of hexadecyloxypropyl-cidofovir (HDP-CDV) as an intravitreal long-lasting delivery system

“…With the current ex vivo infusate, the sample was only subjected to HDP-CDV detection. Based on our previous publication, CDV and various metabolites are possibly present in the infusate and some of metabolites may not be qualified [18, 35]. Therefore, instead of characterizing metabolites in vitro we conducted in vivo efficacy studies to evaluate this drug delivery system.…”