title: Preparation, characterization and pharmacokinetics of Amoitone B-loaded long circulating nanostructured lipid carriers.
abstract: Amoitone B, chemically synthesized as the derivative of Cytosporone B, is a powerful agonist for Nur77 receptor. It has outstanding anticancer activity in vivo. However, the water-insolubility and short biological half-life lead to poor bioavailability, which limits its application. The aim of this study was to develop polyethylene glycol-coated Amoitone B-loaded nanostructured lipid carriers (AmB-PEG-NLC) for parenteral delivery of Amoitone B to prolong drug circulation time in body and enhance the bioavailability. AmB-PEG-NLC were prepared by emulsion-evaporation and low temperature-solidification method, while Amoitone B-loaded NLC (AmB-NLC) were also prepared as control. The characteristics of AmB-PEG-NLC and AmB-NLC such as particle size, zeta potential, entrapment efficiency and drug loading were investigated in detail. The mean particle size was about 200 nm and the zeta potential value was about -15 mV. The X-ray diffraction analysis demonstrated that Amoitone B was not in crystalline state in NLC (AmB-PEG-NLC and AmB-NLC). Drug release pattern with burst release initially and prolonged release afterwards was obtained in vitro for AmB-PEG-NLC. Furthermore, AmB-PEG-NLC exhibited prolonged MRT (mean residence time) and higher AUC (area under drug concentration-time curve) compared with AmB-NLC as well as Amoitone B solution. These results indicated that AmB-PEG-NLC could be a promising delivery system for Amoitone B to prolong the circulation time in body and thus improve its bioavailability.
authors.affiliation: College of Pharmacy, Shandong University, Jinan 250012, PR China.
authors.forename: Jingjing
authors.initials: J
authors.lastname: Luan
authors.affiliation: College of Pharmacy, Shandong University, Jinan 250012, PR China. Electronic address: zhangdianrui2006@163.com.
authors.forename: Dianrui
authors.initials: D
authors.lastname: Zhang
authors.affiliation: College of Pharmacy, Shandong University, Jinan 250012, PR China.
authors.forename: Leilei
authors.initials: L
authors.lastname: Hao
authors.affiliation: College of Pharmacy, Shandong University, Jinan 250012, PR China.
authors.forename: Lisi
authors.initials: L
authors.lastname: Qi
authors.affiliation: College of Pharmacy, Shandong University, Jinan 250012, PR China.
authors.forename: Xinquan
authors.initials: X
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Shandong University, Jinan 250012, PR China.
authors.forename: Hejian
authors.initials: H
authors.lastname: Guo
authors.affiliation: College of Pharmacy, Shandong University, Jinan 250012, PR China.
authors.forename: Caiyun
authors.initials: C
authors.lastname: Li
authors.affiliation: College of Pharmacy, Shandong University, Jinan 250012, PR China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Guo
authors.affiliation: College of Pharmacy, Shandong University, Jinan 250012, PR China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road, Beijing 100083, PR China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: College of Pharmacy, Shandong University, Jinan 250012, PR China. Electronic address: professorgxzhai@126.com.
authors.forename: Guangxi
authors.initials: G
authors.lastname: Zhai
mesh_terms: D061605:Administration, Intravenous; D000818:Animals; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D008055:Lipids / Q000737:chemistry*; D049329:Nanostructures / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D010648:Phenylacetates / Q000097:blood / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics*; D011817:Rabbits; D055672:Static Electricity; D014961:X-Ray Diffraction
chemical_list: D004337:Drug Carriers; D008055:Lipids; D010648:Phenylacetates; C531461:cytosporone B; C576231:n-amyl 2-(3,5-dihydroxy-2-(1-nonanoyl)phenyl)acetate
keywords: Amoitone B; In vitro release; Long circulation; Nanostructured lipid carriers; Pharmacokinetics