Enhanced anti-neuroblastoma activity of a fenretinide complexed form after intravenous administration

Roberta Carosio, Vito Pistoia, Isabella Orienti, Franca Formelli, Elena Cavadini, Salvatore Mangraviti, Paolo G. Montaldo, Emanuela Ognio, Laura Emionite, Guendalina Zuccari

Research output: Contribution to journalArticle

Abstract

Objectives The major limitation to successful chemotherapy of neuroblastoma (NB) is the toxicity and the poor bioavailability of traditional drugs. Methods We synthesised an amphiphilic dextrin derivative (DX-OL) able to host fenretinide (4-HPR) by complexation. In this study, we have investigated the effects of 4-HPR-loaded amphipilic dextrin (DX-OL/4-HPR) in comparison with 4-HPR alone both in vitro on human NB cells and in vivo in pseudometastatic NB models. The haemolysis assay was used as a measure of the potential damage caused by the pharmaceutical formulation in vivo. Pharmacokinetic experiments were performed to assess drug plasma levels in mice treated with free or complexed 4-HPR. Key findings DX-OL/4-HPR exerted a more potent cytotoxic activity on NB cells. Complexed 4-HPR significantly increased the proportion of sub-G1 cells with respect to free 4-HPR. Dextrin derivatives showed no haemolytic activity, indicating their suitability for parenteral administration. DX-OL/4-HPR increased the lifespan and the long-term survival of treated mice over controls. The analysis of drug plasma levels indicates that the complexed drug has a higher AUC due to a reduced clearance from the blood. Conclusions Our data suggest that DX-OL/4-HPR is an injectable formulation that is able to improve drug aqueous solubility and bioavailability.

Original languageEnglish
Pages (from-to)228-236
Number of pages9
JournalJournal of Pharmacy and Pharmacology
Volume64
Issue number2
DOIs
Publication statusPublished - Feb 2012

Fingerprint

Fenretinide
Neuroblastoma
Intravenous Administration
Pharmaceutical Preparations
Biological Availability
Drug Compounding
Hemolysis
Solubility
Area Under Curve

Keywords

  • amphiphilic dextrin derivatives
  • fenretinide
  • neuroblastoma
  • pharmacokinetic and therapeutic experiments

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Carosio, R., Pistoia, V., Orienti, I., Formelli, F., Cavadini, E., Mangraviti, S., ... Zuccari, G. (2012). Enhanced anti-neuroblastoma activity of a fenretinide complexed form after intravenous administration. Journal of Pharmacy and Pharmacology, 64(2), 228-236. https://doi.org/10.1111/j.2042-7158.2011.01403.x

Enhanced anti-neuroblastoma activity of a fenretinide complexed form after intravenous administration. / Carosio, Roberta; Pistoia, Vito; Orienti, Isabella; Formelli, Franca; Cavadini, Elena; Mangraviti, Salvatore; Montaldo, Paolo G.; Ognio, Emanuela; Emionite, Laura; Zuccari, Guendalina.

In: Journal of Pharmacy and Pharmacology, Vol. 64, No. 2, 02.2012, p. 228-236.

Research output: Contribution to journalArticle

Carosio, R, Pistoia, V, Orienti, I, Formelli, F, Cavadini, E, Mangraviti, S, Montaldo, PG, Ognio, E, Emionite, L & Zuccari, G 2012, 'Enhanced anti-neuroblastoma activity of a fenretinide complexed form after intravenous administration', Journal of Pharmacy and Pharmacology, vol. 64, no. 2, pp. 228-236. https://doi.org/10.1111/j.2042-7158.2011.01403.x
Carosio, Roberta ; Pistoia, Vito ; Orienti, Isabella ; Formelli, Franca ; Cavadini, Elena ; Mangraviti, Salvatore ; Montaldo, Paolo G. ; Ognio, Emanuela ; Emionite, Laura ; Zuccari, Guendalina. / Enhanced anti-neuroblastoma activity of a fenretinide complexed form after intravenous administration. In: Journal of Pharmacy and Pharmacology. 2012 ; Vol. 64, No. 2. pp. 228-236.
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