A novel approach for systematic delivery of a hydrophobic anti-leukemia agent tamibarotene mediated by nanostructured lipid carrier.

The present work evaluated the feasibility of nanostructured lipid carriers (NLC) for the intravenous delivery of tamibarotene (Am80), a poorly water-soluble drug for the treatment of acute promyelocytic leukemia (APL). The objective of this research was to develop a suitable drug delivery system in vivo which could improve therapeutic efficacy and decrease side effects. The tamibarotene-loaded-NLC (Am80-NLC) nanosuspension was formulated by the method of melt-emulsification at a high temperature and solidified by ice bath. Based on the optimized results of single-factor screening experiment, the Am80-NLC was found to be relatively uniform in size (189.38+/- 8.07 nm) with a narrow poly-dispersity index (PI) (0.27+/-0.02) and a negative zeta potential (-34.69+/-3.05 mV). The average drug entrapment efficiency and loading capacity was 90.85+/- 1.03% and 9.08+/- 0.10%, respectively. The differential scanning calorimetry (DSC) analysis indicated that Am80 was not in crystalline state in Am80-NLC. The in vitro release profile of Am80-NLC possessed a sustained release characteristic and the release behavior was in accordance with the Ritger-Peppas equation. In vivo, after intravenous injection to mice, Am80-NLC showed a longer retention time and higher AUC values compared with the Am80 solution. In addition, biodistribution results clearly demonstrated that Am80-NLC preferentially decreased the drug distribution in kidney and liver of mice after intravenous injection. These results revealed that injectable Am80-NLC may serve as a promising carrier for Am80 to increase therapeutic efficacy on APL and reduce adverse events.