betadex and honokiol

Honokiol (HK), an active compound derived from Magnolia officinalis Rehd. et Wils, possesses many beneficial biological activities for human beings. However, its poor solubility and low bioavailability severely limits its application. In this way, to improve the pharmaceutical properties, the HK was complexed in hydroxypropyl-β-cyclodextrin (HP-β-CD) and its oral bioavailability and antitumor effects were evaluated. The HK/HP-β-CD inclusion complex (1:1) was prepared by saturated aqueous solution method. The inclusion complex (HK-HP-β-CD) obtained had a higher solubility, about 1497 times that of the free HK. The dissolution rate and the oral bioavailability of HK was also significantly higher from inclusion complex than from free HK. Furthermore, the HK-HP-β-CD exhibited higher antitumor activity against Human Hepatoma Cell Line (HepG2) than free HK. More cells were arrested in the sub-G1 phase of the cell cycle and were induced to undergo late apoptosis when treated with the HK-HP-β-CD than when treated with free HK.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; beta-Cyclodextrins; Biphenyl Compounds; Humans; Lignans; Solubility

Retinal neovascularization (NV) is the leading cause of blindness in the majority of ocular diseases. Several treatment approaches have been developed for retinal NV; of these methods, instillation of nanoparticles into the conjunctival sac has shown potential for retinal NV treatment because it does not cause physical damage and is easy to operate.. In this study, honokiol-loaded chitosan/sulfobutylether-β-cyclodextrin nanoparticles (HKCS- NPs) were prepared for ophthalmic drug delivery systems. An inclusion complex of honokiol and sulfobutylether-β-cyclodextrin was used to incorporated insoluble honokiol into chitosan nanoparticles, which were prepared through ionotropic gelation.. HK-CS-NPs featured a spherical surface with a narrow size distribution of polydispersity index less than 0.250, a mean size range of 373-523 nm, a positive surface charge of +19.9 to +24.2 mV, and an entrapment efficiency of 84.92%. In vitro release studies showed an initial burst release phase and a sustained release phase of nanoparticles. Moreover, in vivo study showed that HK-CS-NPs exhibited good ocular tolerability and could improve ophthalmic bioavailability of honokiol. In particular, the maximum concentration of honokiol after administration of HK-CS-NPs was enhanced by 1.65 times compared with that after instillation of the honokiol suspension alone.. This study proposes HK-CS-NPs as a potential ophthalmic delivery system.

Topics: Administration, Ophthalmic; Animals; beta-Cyclodextrins; Biological Availability; Biphenyl Compounds; Chitosan; Drug Delivery Systems; Drug Liberation; Eye; Lignans; Nanoparticles; Particle Size; Rabbits; Surface Properties

This study aimed to prepare and characterize an inclusion complex of honokiol (HNK) with sulfobutyl ether-β-cyclodextrin (SB-β-CD). The inclusion complex (HNK/CD COMP) was prepared utilizing a freeze-drying method. Phase-solubility curves were employed to obtain stability constants and thermodynamic parameters. The phase-solubility diagram showed a typical A(L)-type, indicating that the 1:1 (HNK:SB-β-CD) inclusion complex was formed. The solid inclusion complex was then characterized by differential scanning calorimetry and Fourier transform infrared spectroscopy. Results showed that HNK/CD COMP exhibited a higher drug release rate than free HNK in vitro. A comparative study of the pharmacokinetics between HNK/CD COMP and free HNK was also performed in rats. In vivo results indicated that AUC0-t and Cmax of HNK/CD COMP increased by approximately 158% and 123% compared with those of the free HNK, respectively. These results suggest that SB-β-CD will be potentially useful in the delivery of poorly soluble drugs, such as HNK.

Topics: Animals; beta-Cyclodextrins; Biological Availability; Biphenyl Compounds; Calorimetry, Differential Scanning; Drug Delivery Systems; Drug Liberation; Freeze Drying; Lignans; Male; Rats; Solubility; Spectroscopy, Fourier Transform Infrared

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.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; Antineoplastic Agents, Phytogenic; beta-Cyclodextrins; Biphenyl Compounds; Cell Survival; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Crystallization; Drug Carriers; Drug Compounding; Drug Stability; Hep G2 Cells; Humans; Injections, Intravenous; Lignans; Liposomes; Male; Microscopy, Electron, Transmission; Particle Size; Rats; Rats, Sprague-Dawley; Solubility; Surface Properties; X-Ray Diffraction