Preparation, characterization, pharmacokinetics, and bioactivity of honokiol‐in‐hydroxypropyl‐β‐cyclodextrin‐in‐liposome

Entrapping inclusion complexes in liposomes has been proposed to increase the entrapment efficiency (EE) and stability of liposomes compared with conventional liposomes. In the present study, a stable honokiol‐in‐hydroxypropyl‐β‐cyclodextrin‐in‐liposome (honokiol‐in‐HP‐β‐CD‐in‐liposome) was developed as honokiol delivery system by a novel method. The final molar ratio of honokiol/HP‐β‐CD/lipid was selected as 1:2:2. The mean particle size was 123.5 nm, the zeta potential was −25.6 mV, and the EE was 91.09 ± 2.76%. The release profile in vitro demonstrated that honokiol is released from honokiol‐in‐HP‐β‐CD‐in‐liposome with a sustained and slow speed. Crystallographic study indicated that honokiol was first bound within HP‐β‐CD and then the inclusion complex was encapsulated within liposomes. Honokiol‐in‐HP‐β‐CD‐in‐liposome without freeze dry kept stable for at least 6 months at 4°C. Pharmacokinetic study revealed that honokiol‐in‐HP‐β‐CD‐in‐liposome significantly retarded the elimination and prolonged the residence time in circulating system. The data of bioactivity showed that honokiol‐in‐HP‐β‐CD‐in‐liposome remained similar antiproliferative activity in A549 and HepG2 tumor cells compared to free honokiol. These results suggested that we had successfully prepared honokiol‐in‐HP‐β‐CD‐in‐liposome. The novel honokiol formulation was easy to push industrialization forward and might be a potential carrier for honokiol delivery in tumor chemotherapy. © 2011 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:3357-3364, 2011