Preparation, characterization and pharmacokinetics of Amoitone B-loaded long circulating nanostructured lipid carriers

•Emulsion–evaporation and low temperature-solidification method was used to prepare nanostructured lipid carriers.•High drug loading and sustained release were achieved by nanostructured lipid carriers.•Long circulation was realized by the modification of PEG.•Drug residence time in vivo was extended and the bioavailability of Amoitone B was enhanced by long circulating nanostructured lipid carriers. 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 200nm and the zeta potential value was about −15mV. 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.