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

Abstract

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.

• Authors: Xin Liu, Zhonglan Wang, Ruihua Feng, Yue Hu, Guihua Huang
• Journal: Journal of biomedical nanotechnology (J Biomed Nanotechnol) Vol. 9 Issue 9 Pg. 1586-93 (Sep 2013) ISSN: 1550-7033 [Print] United States
• PMID: 23980506 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Benzoates
• Delayed-Action Preparations
• Lipids
• Nanocapsules
• Tetrahydronaphthalenes
• tamibarotene

Topics

• Animals
• Antineoplastic Agents (administration & dosage, chemistry, pharmacokinetics)
• Benzoates (administration & dosage, chemistry, pharmacokinetics)
• Delayed-Action Preparations (administration & dosage, chemistry, pharmacokinetics)
• Diffusion
• Hydrophobic and Hydrophilic Interactions
• Leukemia (drug therapy, metabolism)
• Lipids (chemistry)
• Metabolic Clearance Rate
• Mice
• Nanocapsules (administration & dosage, chemistry)
• Organ Specificity
• Tetrahydronaphthalenes (administration & dosage, chemistry, pharmacokinetics)
• Tissue Distribution