Towards improved HIV-microbicide activity through the co-encapsulation of NRTI drugs in biocompatible metal organic framework nanocarriers

Marcos-Almaraz, María T.; Gref, Ruxandra; Agostoni, Valentina; Kreuz, Christine; Clayette, Pascal; Serre, Christian; Couvreur, Patrick; Horcajada, Patricia

doi:10.1039/c7tb01933e

Cited by 32 publications

(26 citation statements)

References 25 publications

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“…Herein we demonstrate that enzymatic nanoreactors based on metal–organic frameworks (MOFs) can be potent prodrug activators. MOFs are an emerging platform that demonstrates potential for a number of biotechnological applications, including sensing, imaging, drug delivery, and enzyme encapsulation . Encapsulated enzymes demonstrate well‐preserved catalytic activities .…”

Section: Methodsmentioning

confidence: 99%

Enzyme‐MOF Nanoreactor Activates Nontoxic Paracetamol for Cancer Therapy

et al. 2018

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Prodrug activation, by exogenously administered enzymes, for cancer therapy is an approach to achieve better selectivity and less systemic toxicity than conventional chemotherapy. However, the short half-lives of the activating enzymes in the bloodstream has limited its success. Demonstrated here is that a tyrosinase-MOF nanoreactor activates the prodrug paracetamol in cancer cells in a long-lasting manner. By generating reactive oxygen species (ROS) and depleting glutathione (GSH), the product of the enzymatic conversion of paracetamol is toxic to drug-resistant cancer cells. Tyrosinase-MOF nanoreactors cause significant cell death in the presence of paracetamol for up to three days after being internalized by cells, while free enzymes totally lose activity in a few hours. Thus, enzyme-MOF nanocomposites are envisioned to be novel persistent platforms for various biomedical applications.

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Section: Methodsmentioning

confidence: 99%

Enzyme‐MOF Nanoreactor Activates Nontoxic Paracetamol for Cancer Therapy

et al. 2018

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“…19,20 In most of these examples modest to low drug loading contents, usually oscillating around 5 wt%, are achieved. More effective encapsulation processes have been shown on nanoscale metal-organic frameworks (nano-MOFs) [21][22][23][24] with antiretroviral drug loadings up to 42 wt% 23,25 or in drug solid nanoparticles ( up 70 wt%), obtained using emulsion-templated freezedrying. 26,27 However, and in spite of these pioneering results, questions such as minimization of side effects, biodistribution improvement or the development of novel formulation allowing for the metabolization into a pharmacologically active drug, mainly intracellularly, still represents a real challenge.…”

Section: Introductionmentioning

confidence: 99%

Versatile iron–catechol-based nanoscale coordination polymers with antiretroviral ligand functionalization and their use as efficient carriers in HIV/AIDS therapy

et al. 2019

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“…The development of biodegradable and biocompatible nanocarrier-based formulations for local application of the antiviral peptide might contribute to advancement in HIV therapy, where recent efforts have focused on disease prevention [ 66 , 67 ].…”

Section: Resultsmentioning

confidence: 99%

Lipid Vesicles Loaded with an HIV-1 Fusion Inhibitor Peptide as a Potential Microbicide

et al. 2020

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The effective use of fusion inhibitor peptides against cervical and colorectal infections requires the development of sustained release formulations. In this work we comparatively study two different formulations based on polymeric nanoparticles and lipid vesicles to propose a suitable delivery nanosystem for releasing an HIV-1 fusion inhibitor peptide in vaginal mucosa. Polymeric nanoparticles of poly-d,l-lactic-co-glycolic acid (PLGA) and lipid large unilamellar vesicles loaded with the inhibitor peptide were prepared. Both formulations showed average sizes and polydispersity index values corresponding to monodisperse systems appropriate for vaginal permeation. High entrapment efficiency of the inhibitor peptide was achieved in lipid vesicles, which was probably due to the peptide’s hydrophobic nature. In addition, both nanocarriers remained stable after two weeks stored at 4 °C. While PLGA nanoparticles (NPs) did not show any delay in peptide release, lipid vesicles demonstrated favorably prolonged release of the peptide. Lipid vesicles were shown to improve the retention of the peptide on ex vivo vaginal tissue in a concentration sufficient to exert its pharmacological effect. Thus, the small size of lipid vesicles, their lipid-based composition as well as their ability to enhance peptide penetration on vaginal tissue led us to consider this formulation as a better nanosystem than polymeric nanoparticles for the sustained delivery of the HIV-1 fusion inhibitor peptide in vaginal tissues.

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Towards improved HIV-microbicide activity through the co-encapsulation of NRTI drugs in biocompatible metal organic framework nanocarriers

Abstract: Stable and active nano-formulations of the biocompatible MOF MIL-100(Fe) coencapsulating two anti-HIV drugs are proposed as efficient HIV microbicides.

Cited by 32 publications

References 25 publications

Enzyme‐MOF Nanoreactor Activates Nontoxic Paracetamol for Cancer Therapy

Enzyme‐MOF Nanoreactor Activates Nontoxic Paracetamol for Cancer Therapy

Versatile iron–catechol-based nanoscale coordination polymers with antiretroviral ligand functionalization and their use as efficient carriers in HIV/AIDS therapy

Lipid Vesicles Loaded with an HIV-1 Fusion Inhibitor Peptide as a Potential Microbicide

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