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

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.

Complex polymeric nanomicelles co-delivering doxorubicin and dimethoxycurcumin for cancer chemotherapy

“…(Duan et al., 2013 ; Meric-Bernstam et al., 2021; Fan et al, 2017 ; Chen et al, 2017 ; Elzoghby et al, 2016 ; Luo et al, 2017 ). Based on the abnormal vasculature of the tumor, these nanostructures usually accumulate in tumors through the enhanced permeability and retention (EPR) effect (Han et al., 2020 ; Lin et al., 2021 ). Particularly the polymeric micelles have gained much interest due to the unique self-assembling nature of amphiphilic copolymers (Peng et al., 2008 ; Ma et al., 2017 ; He et al., 2020 ).…”

Synthesis and in vitro evaluation of natural drug loaded polymeric films for cardiovascular applications

“…For instance, magnolol induces cell apoptosis through inhibiting DNA synthesis, by activating autophagy and p53 pathway. 22–25…”

“…For instance, magnolol induces cell apoptosis through inhibiting DNA synthesis, by activating autophagy and p53 pathway. [22][23][24][25] Polyvinyl alcohol (PVA), synthesized via the polymerization of vinyl acetate, is a synthetic hydrophilic, biocompatible and biodegradable polymer. Its physical, chemical, water solubility, reduced cytotoxicity and easy of processing makes it an excellent polymer for biomedical, pharmaceutical and biotechnological field.…”

Honokiol and Magnolol: Insights into Their Antidermatophytic Effects

“…Honokiol (5,3 -diallyl-2,4 -dihydroxybiphenyl) and magnolol (5,5 -diallyl-2,2 -dihydroxybiphenyl) are neolignan isomers, composed of two phenylpropanoid units linked by an aromatic C-C bond (Figure 1). The literature abounds in reports assessing their properties, e.g., anticancer, neuroprotective, cardioprotective, antimicrobial and anti-inflammatory effects [10][11][12][13]. Both compounds have good safety profiles, with no reported mutagenic or genotoxic effects [14].…”