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M Toyoguchi, L Cheng, KY Hostetler, MF Gardner, JR Beadle, N Rodanant, G Bergeron-Lynn, WR Freeman; Free Ganciclovir Release from Different Formulations of 1-O-Hexadecylpropanediol-3-Phospho-Ganciclovir (HDP-P-GCV) . Invest. Ophthalmol. Vis. Sci. 2002;43(13):1850.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To determine the optimal formulation of lipid prodrug, HDP-P-GCV, for intravitreal delivery. Methods: An equal dose of HDP-P-GCV in dry powder or liposomes was added to rabbit vitreous, human plasma, and heat-inactivated rabbit vitreous in vitro. The samples were incubated at 37ºC for one week. Aliquots were taken from the samples at day 1, 2, 3, and 7 and aliquots were subjected to HPLC analysis of GCV concentration. Results: The amount of GCV released from dry powder of HDP-P-GCV in vitreous was 19849µM (n=3) at day 1 and 1253248 µM at day 7. Detectable GCV concentration dramatically increased over time. The amount of GCV released from a liposomal formulation of HDP-P-GCV in vitreous was much lower, compared to dry powder formulation (p<0.01), with 667 µM (n=3) at day 1 and 24339 µM at day 7. The GCV concentration in the samples in plasma with dry powder formulation was 863 µM at day 1 and 24821 µM at day 7, which was similar to the liposomal formulation of HDP-P-GCV in vitreuos (p≷0.05). When the powder formulation of HDP-P-GCV was incubated with heat-inactivated vitreous, the detectable GCV concentration was low (22 µM) and didn't increase over time. Conclusion: In vitreous, HDP-P-GCV as a dry powder formulation was converted to GCV more rapidly than HDP-P-GCV in liposomes.
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