Ferrocifen stealth LNCs and conventional chemotherapy: A promising combination against multidrug-resistant ovarian adenocarcinoma

Idlas, Pierre; Ladaycia, Abdallah; Némati, Fariba; Lepeltier, Élise; Pigeon, Pascal; Jaouen, Gérard; Decaudin, Didier; Passirani, Catherine

doi:10.1016/j.ijpharm.2022.122164

Cited by 2 publications

(6 citation statements)

References 48 publications

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“…The maximal DL for P722 was 7.0 mg/g of lipophilic excipients. This was a low amount compared to another potent ferrocifen, P53 , for which the maximal DL was 43.6 mg/g, and this was recently explained by the higher lipophilicity of P53 compared to P722 …”

Section: Resultsmentioning

confidence: 92%

“…To the best of our knowledge, it is the first time that a structure–drug delivery system relationship has been demonstrated for ferrocifens. Knowing that ovarian cancer metastases mostly in the peritoneal cavity, together with the remarkable in vivo efficacy on several cancers of P722 (glioblastoma, metastatic melanoma, and ovarian cancer), we can see new opportunities for the use of P769 –LNC gels as local therapies to combat glioblastomas or peritoneal metastatic ovarian cancers.…”

Section: Discussionmentioning

confidence: 99%

“…Molecular structures of the succinimido-ferrocifens under study and of earliest ferrocifens ( P15 and P53 ).…”

Section: Introductionmentioning

confidence: 99%

“…They are composed of a liquid oily core and a polyethylene glycol (PEG) hydroxystearate surfactant shell. Recent studies have highlighted the successful encapsulation of diphenol P722 in LNCs, with promising in vivo results on metastatic melanoma, glioblastoma, and epithelial ovarian cancer. − However, compared to other ferrocifens, drug loading (DL) of this compound in LNCs remains particularly weak.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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Ferrocifens, lipophilic organometallic complexes, comprise a biologically active redox motif [ferrocenyl-ene-pphenol] 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 IC 50 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.

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Section: Resultsmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

“…Molecular structures of the succinimido-ferrocifens under study and of earliest ferrocifens ( P15 and P53 ).…”

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2023

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“…Sci. 2023, 24,12288 Figure 1. Representation of a β-cyclodextrin (CD, here 2-Me-βCD belonging to the ca defined CDs) with the oxygen atom numbering used for our modelling and database bering is not displayed).…”

Section: Introduction 1cyclodextrinsmentioning

confidence: 99%

Unravelling the Role of Uncommon Hydrogen Bonds in Cyclodextrin Ferrociphenol Supramolecular Complexes: A Computational Modelling and Experimental Study

Pigeon,

Najlaoui,

McGlinchey

et al. 2023

IJMS

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We sought to determine the cyclodextrins (CDs) best suited to solubilize a patented succinimido-ferrocidiphenol (SuccFerr), a compound from the ferrociphenol family having powerful anticancer activity but low water solubility. Phase solubility experiments and computational modelling were carried out on various CDs. For the latter, several CD-SuccFerr complexes were built starting from combinations of one or two CD(s) where the methylation of CD oxygen atoms was systematically changed to end up with a database of ca. 13 k models. Modelling and phase solubility experiments seem to indicate the predominance of supramolecular assemblies of SuccFerr with two CDs and the superiority of randomly methylated β-cyclodextrins (RAMEβCDs). In addition, modelling shows that there are several competing combinations of inserted moieties of SuccFerr. Furthermore, the models show that ferrocene can contribute to high stabilization by making atypical hydrogen bonds between Fe and the hydroxyl groups of CDs (single bond with one OH or clamp with two OH of the same glucose unit).

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Ferrocifen stealth LNCs and conventional chemotherapy: A promising combination against multidrug-resistant ovarian adenocarcinoma

Cited by 2 publications

References 48 publications

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

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

Unravelling the Role of Uncommon Hydrogen Bonds in Cyclodextrin Ferrociphenol Supramolecular Complexes: A Computational Modelling and Experimental Study

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