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

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

Reference values of blood cell counts in the first days of life.

The lack of updated neonatal reference values for hematological parameters impacts significantly with clinical management of both healthy and sick newborns. The present pilot study was thus aimed at assessing updated hematological Italian reference values in late preterm and term newborns. From January 2004 to December 2008 hematological laboratory tests were performed in 1175 newborns (820 healthy and 355 sick controls) between 33-41 weeks of gestation, during the first four days after birth. Hematological parameters were sorted for gender and gestational age and statistically analyzed. No gender-related differences were observed at different weeks of gestation and no significant differences were found when study population was sub-grouped for late preterm and term newborns. During the first 4 days of life erythrocytes and platelets remained stable whilst white blood cell counts and differentials were significantly modified. This study shares updated reference values for hematological parameters in the early phases after birth and offers additional support for improving the management of sick infants

Reference values of blood cell counts in the first days of life

The lack of updated neonatal reference values for hematological parameters impacts significantly with clinical management of both healthy and sick newborns. The present pilot study was thus aimed at assessing updated hematological Italian reference values in late preterm and term newborns. From January 2004 to December 2008 hematological laboratory tests were performed in 1175 newborns (820 healthy and 355 sick controls) between 33-41 weeks of gestation, during the first four days after birth. Hematological parameters were sorted for gender and gestational age and statistically analyzed. No gender-related differences were observed at different weeks of gestation and no significant differences were found when study population was sub-grouped for late preterm and term newborns. During the first 4 days of life erythrocytes and platelets remained stable whilst white blood cell counts and differentials were significantly modified. This study shares updated reference values for hematological parameters in the early phases after birth and offers additional support for improving the management of sick infants