{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Vinck R"],"funding":["Agence Nationale de la Recherche","Swedish Research Council","Labex Action"],"pagination":["14611"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9735573"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["23(23)"],"pubmed_abstract":["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)-<i>block</i>-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."],"journal":["International journal of molecular sciences"],"pubmed_title":["In Vivo Sustained Release of the Retrograde Transport Inhibitor Retro-2.1 Formulated in a Thermosensitive Hydrogel."],"pmcid":["PMC9735573"],"funding_grant_id":["ANR-10-LABX-33","ANR-20-CE18-0016-01","K2015-99X-22877-01-6","ANR-14-CE16-0004"],"pubmed_authors":["Pruvost A","Munier M","Cintrat JC","Caramelle L","Vinck R","Nguyen LA","Karpman D","Gillet D","Barbier J"],"additional_accession":[]},"is_claimable":false,"name":"In Vivo Sustained Release of the Retrograde Transport Inhibitor Retro-2.1 Formulated in a Thermosensitive Hydrogel.","description":"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)-<i>block</i>-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":{"release":"2022-01-01T00:00:00Z","publication":"2022 Nov","modification":"2025-04-05T10:33:47.331Z","creation":"2025-04-05T10:33:47.331Z"},"accession":"S-EPMC9735573","cross_references":{"pubmed":["36498939"],"doi":["10.3390/ijms232314611"]}}