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A. Vadlapudi, S. K. Samantha, A. K. Mitra; Evaluation of Novel Targeted Lipid Prodrug Strategy to Improve the Cellular Absorption of Acyclovir. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5129.
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To design and evaluate a novel targeted lipid prodrug delivery system to improve the corneal permeation of acyclovir in treatment of herpes keratitis.
Biotin-Ricinoleicacid-Acyclovir (B-R-ACV), Valine-Ricinoleicacid-Acyclovir, (V-R-ACV), Biotin-ACV (B-ACV) and Ricinoleicacid-ACV (R-ACV) prodrugs were synthesized and characterized using NMR and LC-MS/MS. Ricinoleicacid is the lipophilic moiety. Biotin and Valine are targeting molecules targeting biotin and peptide transporters respectively. Uptake studies were conducted across Caco-2 and MDR1 transfected MDCK model cell lines to assess the feasibility of this approach. To delineate the individual effects of the targeting and the lipid moiety on the prodrug properties, B-ACV and R-ACV were also included in the uptake study. ACV was used as positive control. Samples were analyzed using LC-MS/MS.
All the compounds were synthesized successfully and confirmed by LC-MS/MS and NMR. B-R-ACV has tremendously improved the uptake of ACV. The percentage uptake of B-R-ACV was about 9 times higher as compared to parent drug (ACV). B-ACV and R-ACV have also improved the uptake up to 2-3 times higher relative to ACV.
B-R-ACV, B-ACV and R-ACV have significantly improved the cellular uptake of ACV. However the uptake with B-R-ACV was much higher than B-ACV and R-ACV indicating that both the carrier molecule and the lipid moiety act synergistically towards cellular uptake.
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