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Article Dans Une Revue International Journal of Molecular Sciences Année : 2022

In Vivo Sustained Release of the Retrograde Transport Inhibitor Retro-2.1 Formulated in a Thermosensitive Hydrogel

Robin Vinck
Mathilde Munier
  • Fonction : Auteur
Lucie Caramelle
  • Fonction : Auteur
Diana Karpman
Alain Pruvost
Jean-Christophe Cintrat
Daniel Gillet

Résumé

A recently developed inhibitor of retrograde transport, namely Retro-2.1, proved to be a potent and broad-spectrum lead in vitro against intracellular pathogens, such as toxins, parasites, intracellular bacteria and viruses. To circumvent its low aqueous solubility, a formulation in poly(ethylene glycol)-block-poly(D,L)lactide micelle nanoparticles was developed. This formulation enabled the study of the pharmacokinetic parameters of Retro-2.1 in mice following intravenous and intraperitoneal injections, revealing a short blood circulation time, with an elimination half-life of 5 and 6.7 h, respectively. To explain the poor pharmacokinetic parameters, the metabolic stability of Retro-2.1 was studied in vitro and in vivo, revealing fast cytochrome-P-450-mediated metabolism into a less potent hydroxylated analogue. Subcutaneous injection of Retro-2.1 formulated in a biocompatible and bioresorbable polymer-based thermosensitive hydrogel allowed for sustained release of the drug, with an elimination half-life of 19 h, and better control of its metabolism. This study provides a guideline on how to administer this promising lead in vivo in order to study its efficacy.

Dates et versions

hal-04433359 , version 1 (01-02-2024)

Identifiants

Citer

Robin Vinck, Anvi Laetitia Nguyen, Mathilde Munier, Lucie Caramelle, Diana Karpman, et al.. In Vivo Sustained Release of the Retrograde Transport Inhibitor Retro-2.1 Formulated in a Thermosensitive Hydrogel. International Journal of Molecular Sciences, 2022, 23 (23), pp.14611. ⟨10.3390/ijms232314611⟩. ⟨hal-04433359⟩
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