Characterization, pharmacokinetics, tissue distribution and antitumor activity of honokiol submicron lipid emulsions in tumor-burdened mice

Pharmazie. 2013 Jan;68(1):41-6.

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.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacokinetics*
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Area Under Curve
  • Biphenyl Compounds / pharmacokinetics*
  • Biphenyl Compounds / pharmacology*
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid
  • Drug Compounding
  • Drug Stability
  • Electrochemistry
  • Emulsions
  • Hydrogen-Ion Concentration
  • Injections, Intravenous
  • Lignans / pharmacokinetics*
  • Lignans / pharmacology*
  • Mice
  • Neoplasms, Experimental / drug therapy*
  • Neoplasms, Experimental / metabolism*
  • Osmolar Concentration
  • Particle Size
  • Reproducibility of Results
  • Soybean Oil
  • Tissue Distribution

Substances

  • Antineoplastic Agents, Phytogenic
  • Biphenyl Compounds
  • Emulsions
  • Lignans
  • honokiol
  • Soybean Oil