Honokiol/Magnolol-Loaded Self-Assembling Lecithin-Based Mixed Polymeric Micelles (lbMPMs) for Improving Solubility to Enhance Oral Bioavailability
Hong-Liang Lin, Wen-Ting Cheng, Ling-Chun Chen, Hsiu‐O Ho, Shyr-Yi Lin, Chien‐Ming Hsieh
Abstract
Objective: This study was intended to utilize lecithin-based mixed polymeric micelles ( lb MPMs) 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 lb MPMs, 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 lb MPMs formulations composed of honokiol/magnolol:lecithin:NaDOC ( lb MPMs[NaDOC]) and honokiol/magnolol:lecithin:PP123 ( lb MPMs[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 lb MPMs 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 lb MPMs[NaDOC] showed much improvement in enhancing bioavailability than that by lb MPMs[PP123] for both honokiol and magnolol. The absolute bioavailability for honokiol and magnolol after intravenous administration of lb MPMs[NaDOC] exhibited 0.93- and 3.4-fold increases, respectively, compared to that of free honokiol and magnolol. For oral administration with lb MPMs[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 lb MPMs[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: lecithin, mixed polymeric micelles, honokiol, magnolol, sodium deoxycholate, pluronic