Physicochemical Characterization of Ferrocifen Lipid Nanocapsules: Customized Drug Delivery Systems Guided by the Molecular Structure - ENS - École normale supérieure Accéder directement au contenu
Article Dans Une Revue Langmuir Année : 2023

Physicochemical Characterization of Ferrocifen Lipid Nanocapsules: Customized Drug Delivery Systems Guided by the Molecular Structure

Résumé

Ferrocifens, lipophilic organometallic complexes, comprise a biologically active redox motif [ferrocenyl-ene-p-phenol] which confers very interesting cytotoxic properties to this family. However, because of their highly lipophilic nature, a formulation stage is required before being administered in vivo. In recent decades, ferrocifen lipid nanocapsules (LNCs) have been successfully formulated and have demonstrated anticancer activity on multidrug-resistant cancers in several mice and rat models (glioblastoma, breast cancer, and metastatic melanoma). A recent family of ferrocifens (succinimidoalkyl-ferrociphenols, including P722) appears to be most efficacious on several resistant cancer cell lines, with IC50 values in the nanomolar range together with promising in vivo results on murine ovarian cancer models. As LNCs are composed of an oily core (caprylic/capric triglycerides), modulation of the succinimido-ferrociphenol lipophilicity could be a valuable approach toward improving the drug loading in LNCs. As the drug loading of the diphenol P722 in LNCs was low, it was structurally modified to increase its lipophilicity and thereby the payload in LNCs. Chemical modification led to a series of five succinimido-ferrocifens. Results confirmed that these slight structural modifications led to increased drug loading in LNCs for all ferrocifens, with no reduction of their cytotoxicity on the SKOV3 ovarian cancer cell line. Interestingly, encapsulation of two of the ferrocifens, diester P769 and monophenolic ester (E)-P998, led to the formation of a gel. This was unprecedented behavior, a phenomenon that could be rationalized in terms of the positioning of ferrocifens in LNCs as shown by the decrease of interfacial tension measurements at the water/oil interface. Moreover, these results highlighted the importance of obtaining a gel of this particular motif, in which the acetylated phenolic ring and the succinimidoalkyl moieties are mutually cis relative to the central double bond. Promising perspectives to use these ferrocifen-loaded LNCs to treat glioblastoma could be readily envisaged by local application of the gel in the cavity after tumor resection.

Domaines

Chimie
Fichier principal
Vignette du fichier
Idlas_2023_Physico-chemical characterization of ferrocifen lipid nanocapsules_customized drug delivery systems guided by the molecular structure.pdf (1.14 Mo) Télécharger le fichier
Idlas_2023_suppl_Physico-chemical characterization of ferrocifen lipid nanocapsules_customized drug delivery systems guided by the molecular structure.pdf (1.25 Mo) Télécharger le fichier
Origine : Fichiers produits par l'(les) auteur(s)

Dates et versions

hal-03955374 , version 1 (02-02-2023)

Identifiants

Citer

Pierre Idlas, Elise Lepeltier, Guillaume Bastiat, Pascal Pigeon, Michael Mcglinchey, et al.. Physicochemical Characterization of Ferrocifen Lipid Nanocapsules: Customized Drug Delivery Systems Guided by the Molecular Structure. Langmuir, 2023, 39 (5), pp.1885-1896. ⟨10.1021/acs.langmuir.2c02910⟩. ⟨hal-03955374⟩
71 Consultations
225 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More