title: Characterization, pharmacokinetics, tissue distribution and antitumor activity of honokiol submicron lipid emulsions in tumor-burdened mice.
abstract: Honokiol, isolated from the Chinese traditional herb magnolia, is a poorly water-soluble component and has been found to have anti-tumor properties. In the current study, honokiol submicron lipid emulsions (HK-SLEs) were prepared by high pressure homogenization technology. After HK-SLEs were physically characterized, their pharmacokinetics, tissue distribution and antitumor activity after intravenous (i.v.) administration to tumor-burdened mice were examined, using honokiol solution (HK-SOL) as the control. The results showed that the mean particle size, zeta potential, pH value, osmolality, drug loading (DL)% and entrapment efficiency (EE)% of HK-SLEs were 186.6 +/- 1.7 nm, -35.65 +/- 0.67 mV, 7.22 +/- 0.26, 298 +/- 2.3 mOsm/L, 7.1 +/- 0.2% and 95.5 +/- 0.2%, respectively. HK-SLEs were stable for at least 12 months when stored at 4 +/- 2 degrees C. The pharmacokinetic results showed that the drug concentration-time curves of HK-SLEs and HK-SOL could both be described by an open two-compartment model. The half-life of HK-SLEs (t1/2(alpha) = 8.014 min, t1/2(beta) = 35.784 min) was remarkably prolonged compared to that of HK-SOL (t1/2(alpha) = 4.318 min, t1/2(beta) = 15.522 min). HK-SLEs exhibited a greater AUC and reduced plasma clearance. The tissue distribution results indicated that HK-SLEs have better targeting properties to lung and tumor tissues compared with those of HK-SOL. Both HK-SLEs and HK-SOL tended to accumulate in brain tissue. In vivo study showed that HK-SLEs treatment caused significant inhibition of mouse sarcoma S180 tumor growth compared to HK-SOL. These results suggest that HK-SLEs might be an effective parenteral carrier for honokiol delivery in cancer treatment.
authors: School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China.
authors: Jiaxin
authors: J
authors: Zheng
authors: Yujie
authors: Y
authors: Tang
authors: Moran
authors: M
authors: Sun
authors: Yuanyuan
authors: Y
authors: Zhao
authors: Qiang
authors: Q
authors: Li
authors: Jie
authors: J
authors: Zhou
authors: Yanzhi
authors: Y
authors: Wang
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics* / Q000494:pharmacology*; D019540:Area Under Curve; D001713:Biphenyl Compounds / Q000493:pharmacokinetics* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding; D004355:Drug Stability; D004563:Electrochemistry; D004655:Emulsions; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D017705:Lignans / Q000493:pharmacokinetics* / Q000494:pharmacology*; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism*; D009994:Osmolar Concentration; D010316:Particle Size; D015203:Reproducibility of Results; D013024:Soybean Oil; D014018:Tissue Distribution; D000498:Allyl Compounds; D010636:Phenols
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D001713:Biphenyl Compounds; D004655:Emulsions; D017705:Lignans; D013024:Soybean Oil; C005499:honokiol; D000498:Allyl Compounds; D010636:Phenols