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Towards an improved anti-HIV activity through the co-encapsulation of NRTI drugs in biocompatible Metal Organic Frameworks nanocarriers

Abstract

The efficacy of the routinely used anti-HIV (Human Immunodeficiency Virus) therapy based on nucleoside reverse transcriptase inhibitors (NRTIs) is limited by the poor cellular uptake of their active triphosphorylated metabolites and the low efficiency of intracellular phosphorylation of their prodrugs. Nanoparticles of iron(III) polycarboxylate Metal-Organic Frameworks (nanoMOFs) are promising drug nanocarriers. In this study, two active triphosphorylated NRTIs, the azidothymidine triphosphate (AZT-Tp) and lamivudine triphosphate (3TC-Tp), were successfully co-encapsulated into the biocompatible mesoporous iron(III) trimesate MIL-100(Fe) nanoMOF in order to improve anti-HIV therapies. Drug loaded nanoMOFs could be stored up to 2-months and reconstituted after freeze drying, keeping similar physicochemical properties. Their antiretroviral activity was evidenced in vitro on monocyte-derived macrophages experimentally infected with HIV, making these co-encapsulated nanosystems excellent HIV-microbicide candidates.

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Publication details

The article was received on 18 Jul 2017, accepted on 29 Sep 2017 and first published on 29 Sep 2017


Article type: Paper
DOI: 10.1039/C7TB01933E
Citation: J. Mater. Chem. B, 2017, Accepted Manuscript
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    Towards an improved anti-HIV activity through the co-encapsulation of NRTI drugs in biocompatible Metal Organic Frameworks nanocarriers

    M. T. Marcos Almaraz, R. Gref, V. Agostoni, C. kreuz, P. Clayette , C. Serre, P. Couvreur and P. Horcajada, J. Mater. Chem. B, 2017, Accepted Manuscript , DOI: 10.1039/C7TB01933E

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