title: Novel PEG-grafted nanostructured lipid carrier for systematic delivery of a poorly soluble anti-leukemia agent Tamibarotene: characterization and evaluation.
abstract: Tamibarotene (Am80), a poorly water-soluble drug for the treatment of acute promyelocytic leukemia (APL), loaded nanostructured lipid carrier (Am80-NLC) was developed and characterized previously. The purpose of the present work was to develop PEGylated nanostructured lipid carrier (PEG-NLC) for intravenous delivery of Am80, with the aim to further extend the circulation in blood and decrease the adverse events. Am80-loaded PEG-NLC (Am80-PEG-NLC) modified with PEG-40 stearate (PEG40-SA, molecular weight 2000 Da) was formulated by the method of melt-emulsification and low temperature-solidification technique. Am80-NLC was developed as well as control. Based on the optimized results of single-factor screening experiment, the average drug entrapment efficiency, the mean particle size, and zeta potential of Am80-NLC and Am80-PEG-NLC were found to be 89.8-94.3%, 178.9-201.6 nm, and -37.74 to -20.1 mV, respectively. In vitro drug release of Am80-NLC and Am80-PEG-NLC possessed a sustained release characteristic and their release behavior was in accordance with the Ritger-Peppas equation. In vivo, after intravenous (i.v.) injection to rats, the mean residence time (MRT) of Am80-PEG-NLC group was significantly prolonged and the AUC value was improved as well compared with the Am80-NLC group. Furthermore, the biodistribution in mice showed that Am80-PEG-NLC preferentially decreased the accumulation of Am80 in kidney and increased the drug concentration in brain after i.v. injection. In conclusion, Am80-PEG-NLC may be a potential delivery system for Am80 in the treatment of APL.
authors.affiliation: The School of Pharmaceutical Science, Shandong University , Ji'nan, Shandong Province , PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Zhang
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Jiang
authors.forename: Yue
authors.initials: Y
authors.lastname: Hu
authors.forename: Zhonglan
authors.initials: Z
authors.lastname: Wang
authors.forename: Junli
authors.initials: J
authors.lastname: Liu
authors.forename: Ruihua
authors.initials: R
authors.lastname: Feng
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Guihua
authors.initials: G
authors.lastname: Huang
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D001565:Benzoates / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D004339:Drug Compounding; D016503:Drug Delivery Systems; D006207:Half-Life; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D054709:Lecithins / Q000737:chemistry*; D015473:Leukemia, Promyelocytic, Acute / Q000188:drug therapy; D051379:Mice; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011092:Polyethylene Glycols / Q000737:chemistry*; D011897:Random Allocation; D017208:Rats, Wistar; D012995:Solubility; D013499:Surface Properties; D013764:Tetrahydronaphthalenes / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D001565:Benzoates; D004337:Drug Carriers; D054709:Lecithins; C000589418:PEG 40 monostearate; D013764:Tetrahydronaphthalenes; C061133:tamibarotene; D011092:Polyethylene Glycols
keywords: Biodistribution; PEGylated; Tamibarotene; intravenous delivery; nanostructured lipid carrier; pharmacokinetic