Honokiol/Magnolol-Loaded Self-Assembling Lecithin-Based Mixed Polymeric Micelles (lb MPMs) for Improving Solubility to Enhance Oral Bioavailability

Int J Nanomedicine. 2021 Jan 26:16:651-665. doi: 10.2147/IJN.S290444. eCollection 2021.

Abstract

Objective: This study was intended to utilize lecithin-based mixed polymeric micelles (lbMPMs) for enhancing the solubility and bioavailability of honokiol and magnolol to resolve the hindrance of their extreme hydrophobicity on the clinical applications.

Methods: Lecithin was selected to increase the volume of the core of lbMPMs, thereby providing a greater solubilization capacity. A series of amphiphilic polymers (sodium deoxycholate [NaDOC], Cremophor®, and Pluronic® series) were included with lecithin for screening and optimization.

Results: After preliminary evaluation and subsequentially optimization, two lbMPMs formulations composed of honokiol/magnolol:lecithin:NaDOC (lbMPMs[NaDOC]) and honokiol/magnolol:lecithin:PP123 (lbMPMs[PP123]) in respective ratios of 6:2:5 and 1:1:10 were optimally obtained with the mean particle sizes of 80-150 nm, encapsulation efficacy (EEs) of >90%, and drug loading (DL) of >9.0%. These lbMPMs efficiently stabilized honokiol/magnolol in phosphate-buffered saline (PBS) at room temperature or 4 °C and in fetal bovine serum or PBS at 37 °C. PK study demonstrated that lbMPMs[NaDOC] showed much improvement in enhancing bioavailability than that by lbMPMs[PP123] for both honokiol and magnolol. The absolute bioavailability for honokiol and magnolol after intravenous administration of lbMPMs[NaDOC] exhibited 0.93- and 3.4-fold increases, respectively, compared to that of free honokiol and magnolol. For oral administration with lbMPMs[NaDOC], the absolute bioavailability of honokiol was 4.8%, and the absolute and relative bioavailability of magnolol were 20.1% and 2.9-fold increase, respectively.

Conclusion: Overall, honokiol/magnolol loaded in lbMPMs[NaDOC] showed an improvement of solubility with suitable physical characteristics leading to enhance honokiol and magnolol bioavailability and facilitating their wider application as therapeutic agents for treating human disorders.

Keywords: honokiol; lecithin; magnolol; mixed polymeric micelles; pluronic; sodium deoxycholate.

MeSH terms

  • Administration, Oral
  • Animals
  • Biological Availability
  • Biphenyl Compounds / blood
  • Biphenyl Compounds / chemistry
  • Biphenyl Compounds / pharmacokinetics
  • Biphenyl Compounds / pharmacology*
  • Drug Liberation
  • Humans
  • Lecithins / chemistry*
  • Lignans / blood
  • Lignans / chemistry
  • Lignans / pharmacokinetics
  • Lignans / pharmacology*
  • Male
  • Micelles*
  • Particle Size
  • Polymers / chemistry*
  • Rats
  • Rats, Sprague-Dawley
  • Solubility

Substances

  • Biphenyl Compounds
  • Lecithins
  • Lignans
  • Micelles
  • Polymers
  • magnolol
  • honokiol