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A novel oral micellar fenretinide formulation with enhanced bioavailability and antitumour activity against multiple tumours from cancer stem cells.
- Source :
-
Journal of experimental & clinical cancer research : CR [J Exp Clin Cancer Res] 2019 Aug 22; Vol. 38 (1), pp. 373. Date of Electronic Publication: 2019 Aug 22. - Publication Year :
- 2019
-
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.<br />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.<br />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.<br />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.
- Subjects :
- Administration, Oral
Animals
Antineoplastic Agents administration & dosage
Antineoplastic Agents chemistry
Antineoplastic Agents pharmacokinetics
Apoptosis
Biological Availability
Cell Proliferation
Colonic Neoplasms metabolism
Colonic Neoplasms pathology
Female
Fenretinide chemistry
Fenretinide pharmacokinetics
Humans
Lung Neoplasms metabolism
Lung Neoplasms pathology
Melanoma metabolism
Melanoma pathology
Mice
Mice, Inbred NOD
Mice, SCID
Neoplastic Stem Cells metabolism
Neoplastic Stem Cells pathology
Tissue Distribution
Tumor Cells, Cultured
Xenograft Model Antitumor Assays
Colonic Neoplasms drug therapy
Fenretinide administration & dosage
Lung Neoplasms drug therapy
Melanoma drug therapy
Micelles
Neoplastic Stem Cells drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1756-9966
- Volume :
- 38
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Journal of experimental & clinical cancer research : CR
- Publication Type :
- Academic Journal
- Accession number :
- 31439019
- Full Text :
- https://doi.org/10.1186/s13046-019-1383-9