OCULAR DISPOSITION OF ACYCLOGUANOSINE ANALOGUES

..This cell line may thus be used as an effective screening tool for intravitreally administered drugs/prodrugs targeted toward MCT1 expressed on the RPE...

..Such facilitated absorption of prodrugs may be a result of a combination of transcellular passive diffusion and peptide transporter (PEPT1)-mediated transport across the corneal epithelium...

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..In this review article, the authors discuss various drug delivery strategies, devices and challenges associated with drug delivery to the retina...

..The purpose of this study is to elucidate the functional activity of large neutral amino acid transporter (LAT) in rabbit retina and to delineate its role in the retinal uptake and intravitreal pharmacokinetics of L-phenylalanine (L-Phe)...

..The overall aim of this research work was to evaluate a series of dipeptide monoester prodrugs of an antiviral agent, ganciclovir (GCV), for oligopeptide transporter-targeted transscleral drug delivery to rabbit retina...

..This article provides an insight into low and variable oral bioavailability and related complications leading to loss of therapeutic activity of MDR and CYP 450 substrates...

..This research work demonstrated, for the first time, the functional and molecular existence of a specialized high affinity carrier-mediated system for folic acid uptake, in human retinoblastoma cells...

..To evaluate in vivo corneal absorption of the amino acid prodrugs of acyclovir (ACV) using a topical well model and microdialysis in rabbits...

..This strategy improved both the cellular permeability and the amount of intact prodrug transported which would enable targeting the nutrient transporters at blood ocular barrier (BOB)...

..The amino acid ester prodrug SACV owing to its enhanced stability, higher AUC and better concentration at last time point seems to be a promising candidate for the oral treatment of herpes infections...

..Current momentum in the invention of new drug delivery systems hold a promise towards much improved therapies for the treatment of vision threatening disorders...

..The objectives were (i) to test in vivo functional activity of MRP2 on rabbit corneal epithelium and (ii) to evaluate modulation of P-gp and MRP2 mediated efflux of erythromycin when co-administered with corticosteroids...

..As a whole, this article is intended to provide a valuable insight into current trends in the field of ocular drug delivery and highlights advances made in patent literature...

..The objective of this study was to explore physical barriers for ocular drug absorption and to verify the presence and possible role of BCRP as a barrier for ocular drug resistance...

..Study also aims to delineate the vitreal pharmacokinetics of biotin-GCV...

..A-->B transport of [(3)H]-cyclosporine-A was elevated in the presence of MK-571 in freshly excised rabbit cornea indicating potential role of this efflux transporter and high clinical significance of this finding...

..Results from these studies suggest the application of MDCKII-MDR1 cell line as a rapid effective tool to study peptide mediated influx of compounds that may be substrates for both P-gp and peptide transporters...

..For the first time we have demonstrated high expression of MRP-2 in rabbit corneal epithelium and its functional activity causing drug efflux. RT-PCR, immunoprecipitation followed by Western blot analysis further confirms the result...

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..In conclusion, this study reports the development of PLGA microspheres with high payloads and their PLGA-PEG-PLGA gel based formulations. Drug release equations have been developed that effectively describe the triphasic GCV release...

..In conclusion, the diester GCV prodrugs demonstrated excellent chemical stability, high aqueous solubility and markedly enhanced antiviral potency against the herpes viruses without any increase in cytotoxicity...

..Special problems examined include anterior and posterior ocular clearance mechanisms, intraocular metabolism and active transport of drugs...

..CONCLUSIONS: L-Alanine, the chosen model substrate, was actively transported by Na+-dependent, neutral amino acid exchanger ASCT1, which was identified and functionally characterized on rPCEC cells and rabbit cornea...

..In summary, this review emphasises the urgent need to make changes in drug discovery and drug delivery as efflux pumps and metabolising enzymes play an important role in drug delivery and disposition...

..Polymer blending can effectively alter drug-release rates of controlled delivery systems in the absence of any additives...

..CONCLUSIONS: Val-Val-GCV demonstrates excellent corneal permeability and chemical stability, high aqueous solubility, and substantial in vivo antiviral activity against the HSV-1...

..These studies demonstrated for the first time the existence of a human sodium dependant multivitamin transporter (hSMVT), a specialized carrier-mediated system for biotin uptake, in human derived retinoblastoma cells...

..In conclusion, utility of enzyme inhibitors to modulate transport and metabolism of prodrugs appears to be promising strategy for enhancing drug transport across cornea...

..Enhanced permeabilities of the prodrugs indicate that drug derivatization can be a viable strategy for overcoming P-gp-mediated efflux...

..A saturable, sodium dependent, and pH sensitive transporter with high specificity for L-ascorbic acid was functionally characterized and was identified as SVCT2...

..The dipeptide prodrug GVACV owing to its enhanced absorption of ACV seems to be a promising candidate for the treatment of ocular HSV infections...

..CONCLUSIONS: Considering retinal GCV concentrations generated and vitreal pharmacokinetic profiles, Gly-Val-GCV appears to be a lead candidate for further in vivo evaluation against human cytomegalovirus (HCMV) retinitis...

..Further, the presence of biotin in tears suggests the physiological significance of this transporter in rabbit corneal epithelium...

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