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Journal of Experimental & Clinical Cancer Research
Published in: Journal of Experimental & Clinical Cancer Research 1/2019

Open Access 01-12-2019 | Melanoma | Research

A novel oral micellar fenretinide formulation with enhanced bioavailability and antitumour activity against multiple tumours from cancer stem cells

Authors: Isabella Orienti, Valentina Salvati, Giovanni Sette, Massimo Zucchetti, Lucilla Bongiorno-Borbone, Angelo Peschiaroli, Lello Zolla, Federica Francescangeli, Mariella Ferrari, Cristina Matteo, Ezia Bello, Antonio Di Virgilio, Mario Falchi, Maria Laura De Angelis, Marta Baiocchi, Gerry Melino, Ruggero De Maria, Ann Zeuner, Adriana Eramo

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2019

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Abstract

Background

An increasing number of anticancer agents has been proposed in recent years with the attempt to overcome treatment-resistant cancer cells and particularly cancer stem cells (CSC), the major culprits for tumour resistance and recurrence. However, a huge obstacle to treatment success is the ineffective delivery of drugs within the tumour environment due to limited solubility, short circulation time or inconsistent stability of compounds that, together with concomitant dose-limiting systemic toxicity, contribute to hamper the achievement of therapeutic drug concentrations. The synthetic retinoid Fenretinide (4-hydroxy (phenyl)retinamide; 4-HPR) formerly emerged as a promising anticancer agent based on pre-clinical and clinical studies. However, a major limitation of fenretinide is traditionally represented by its poor aqueous solubility/bioavailability due to its hydrophobic nature, that undermined the clinical success of previous clinical trials.

Methods

Here, we developed a novel nano-micellar fenretinide formulation called bionanofenretinide (Bio-nFeR), based on drug encapsulation in an ion-pair stabilized lipid matrix, with the aim to raise fenretinide bioavailability and antitumour efficacy.

Results

Bio-nFeR displayed marked antitumour activity against lung, colon and melanoma CSC both in vitro and in tumour xenografts, in absence of mice toxicity. Bio-nFeR is suitable for oral administration, reaching therapeutic concentrations within tumours and an unprecedented therapeutic activity in vivo as single agent.

Conclusion

Altogether, our results indicate Bio-nFeR as a novel anticancer agent with low toxicity and high activity against tumourigenic cells, potentially useful for the treatment of solid tumours of multiple origin.
Appendix
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Metadata
Title
A novel oral micellar fenretinide formulation with enhanced bioavailability and antitumour activity against multiple tumours from cancer stem cells
Authors
Isabella Orienti
Valentina Salvati
Giovanni Sette
Massimo Zucchetti
Lucilla Bongiorno-Borbone
Angelo Peschiaroli
Lello Zolla
Federica Francescangeli
Mariella Ferrari
Cristina Matteo
Ezia Bello
Antonio Di Virgilio
Mario Falchi
Maria Laura De Angelis
Marta Baiocchi
Gerry Melino
Ruggero De Maria
Ann Zeuner
Adriana Eramo
Publication date
01-12-2019
Publisher
BioMed Central
Published in
Journal of Experimental & Clinical Cancer Research / Issue 1/2019
Electronic ISSN: 1756-9966
DOI
https://doi.org/10.1186/s13046-019-1383-9

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