Liposomal encapsulation of trans-crocetin enhances oxygenation in patients with COVID-19-related ARDS receiving mechanical ventilation.

Fiche publication

Date publication

juin 2021

Journal

Journal of controlled release : official journal of the Controlled Release Society

Auteurs

Membres identifiés du Cancéropôle Est :
Pr PIVOT Xavier , Mme SARTORI Valérie , Pr VELTEN Michel , Dr VILLA Pascal , Dr DETAPPE Alexandre , Dr COLIAT Pierre

Tous les auteurs :
Mertes PM, Collange O, Coliat P, Banerjee M, Diringer MC, Roche A, Delabranche X, Chaban V, Voegelin M, Bernard A, Sartori V, Laurent N, Velten M, Dhindsa N, Defuria J, Kim G, Xu ZH, Theodorou M, Huang ZR, Khalifa K, Geng B, Niyikiza C, Moyo V, Gizzi P, Villa P, Detappe A, Pivot X

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/34175365

Résumé

Current therapeutic treatments improving the impaired transportation of oxygen in acute respiratory distress syndrome (ARDS) have been found to be relevant and beneficial for the therapeutic treatment of COVID-19 patients suffering from severe respiratory complications. Hence, we report the preclinical and the preliminary results of the Phase I/II clinical trial of LEAF-4 L6715, a liposomal nanocarrier encapsulating the kosmotropic agent trans-crocetin (TC), which, once injected, enhance the oxygenation of vascular tissue and therefore has the potential to improve the clinical outcomes of ARDS and COVID-19 in severely impacted patients. We demonstrated that the liposomal formulation enabled to increase from 30 min to 48 h the reoxygenation properties of free TCs in vitro in endothelial cells, but also to improve the half-life of TC by 6-fold in healthy mice. Furthermore, we identified 25 mg/kg as the maximum tolerated dose in mice. This determined concentration led to the validation of the therapeutic efficacy of LEAF-4 L6715 in a sepsis mouse model. Finally, we report the preliminary outcomes of an open-label multicenter Phase I/II clinical trial (EudraCT 2020-001393-30; NCT04378920), which was aimed to define the appropriate schedule and dosage of LEAF-4 L6715 and to confirm its tolerability profile and preliminary clinical activity in COVID-19 patients treated in intensive care unit.