Liposomal encapsulation of trans-crocetin enhances oxygenation in patients with COVID-19-related ARDS receiving mechanical ventilation - Archive ouverte HAL Access content directly
Journal Articles Journal of Controlled Release Year : 2021

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

Paul-Michel Mertes
  • Function : Author
  • PersonId : 1102512
Olivier Collange
  • Function : Author
  • PersonId : 1102511
Pierre Coliat
  • Function : Author
  • PersonId : 1145326
Mainak Banerjee
  • Function : Author
  • PersonId : 1160590
Marie-Charlotte Diringer
  • Function : Author
  • PersonId : 1160591
Anne Roche
  • Function : Author
Nina Laurent
  • Function : Author
Michel Velten
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  • PersonId : 908292
Navreet Dhindsa
  • Function : Author
Jason Defuria
  • Function : Author
Gwangseong Kim
  • Function : Author
Zhenghong Hannah Xu
  • Function : Author
Marina Theodorou
  • Function : Author
Zhaohua Richard Huang
  • Function : Author
Kaniz Khalifa
  • Function : Author
Bolin Geng
  • Function : Author
Clet Niyikiza
  • Function : Author
Victor Moyo
  • Function : Author
Xavier Pivot
  • Function : Author
  • PersonId : 1160594

Abstract

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-4L6715, 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-4L6715 and to confirm its tolerability profile and preliminary clinical activity in COVID-19 patients treated in intensive care unit.
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Origin : Publication funded by an institution

Dates and versions

hal-03767483 , version 1 (01-09-2022)

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Paul-Michel Mertes, Olivier Collange, Pierre Coliat, Mainak Banerjee, Marie-Charlotte Diringer, et al.. Liposomal encapsulation of trans-crocetin enhances oxygenation in patients with COVID-19-related ARDS receiving mechanical ventilation. Journal of Controlled Release, 2021, 336, pp.252-261. ⟨10.1016/j.jconrel.2021.06.033⟩. ⟨hal-03767483⟩
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