title: 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: School of Pharmaceutical Science, Shandong University, 44 Wenhua Xi Road, Ji'nan, 250012, China. LX_liuxin_918@163.com
authors: Xin
authors: X
authors: Liu
authors: Zhonglan
authors: Z
authors: Wang
authors: Ruihua
authors: R
authors: Feng
authors: Yue
authors: Y
authors: Hu
authors: Guihua
authors: G
authors: Huang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D001565:Benzoates / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics*; D004058:Diffusion; D057927:Hydrophobic and Hydrophilic Interactions; D007938:Leukemia / Q000188:drug therapy / Q000378:metabolism; D008055:Lipids / Q000737:chemistry*; D008657:Metabolic Clearance Rate; D051379:Mice; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry*; D009928:Organ Specificity; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D001565:Benzoates; D003692:Delayed-Action Preparations; D008055:Lipids; D053769:Nanocapsules; D013764:Tetrahydronaphthalenes; C061133:tamibarotene