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

Ruggero De Maria Marchiano, Valentina Salvati, Giovanni Sette, Isabella Orienti, 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, Ann Zeuner, Adriana Eramo

Risultato della ricerca: Contributo in rivistaArticolo in rivista

9 Citazioni (Scopus)

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.
Lingua originaleEnglish
pagine (da-a)N/A-N/A
RivistaJOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH
Volume38
DOI
Stato di pubblicazionePubblicato - 2019

Keywords

  • Antitumour activity
  • Bioavailability
  • Cancer stem cells
  • Cancer therapy
  • Drug delivery
  • Fenretinide
  • Pharmacokinetics
  • Solid tumours
  • Solubility

Fingerprint Entra nei temi di ricerca di 'A novel oral micellar fenretinide formulation with enhanced bioavailability and antitumour activity against multiple tumours from cancer stem cells'. Insieme formano una fingerprint unica.

Cita questo