Improved oral bioavailability of magnolol by using a binary mixed micelle system

Abstract

The aim of this study was to prepare two novel magnolol (MO)-loaded binary mixed micelles (MO-M) using biocompatible copolymers of Soluplus (SOL) and Solutol HS15 (HS15), SOL and d-alpha-tocopheryl polyethylene glycol 1000 succinate (TPGS), to improve magnolol's poor solubility and its oral bioavailability. The organic solvent evaporation method was used to obtain two MO-M by optimization; one was prepared by using SOL and HS15 (MO-H), and the other was prepared by using SOL and TPGS (MO-T). The entrapment efficiency (EE%) and drug loading (DL%) of MO-T were 94.61 ± 0.91% and 4.03 ± 0.19%, respectively, and the MO-H has higher EE% and DL% (98.37 ± 1.23%, 4.12 ± 0.16%). TEM results showed that the morphology of MO-M was homogeneous and was spherical in shape. The dilution stability of MO-M did not undergo significant changes. Permeability of MO-M across a Caco-2 cell monolayer was enhanced in Caco-2 cell transport models. The pharmacokinetics study showed that the relative oral bioavailability of MO-T and MO-H increased by 2.39- and 2.98-fold, respectively, compared to that of raw MO. This indicated that MO-H and MO-T could promote absorption of MO in the gastrointestinal tract. Collectively, the mixed micelles demonstrated greater efficacy as a drug delivery system. The development of these novel mixed micelles is valuable for resolving the poor solubility and bioavailability of drugs.

Thymoquinone-Loaded Soluplus®-Solutol® HS15 Mixed Micelles: Preparation, In Vitro Characterization, and Effect on the SH-SY5Y Cell Migration

“…Since mixed Soluplus ® -Solutol ® HS15 micelles (SSM) are a standard and conventional nanoformulations widely used for application in biopharmaceutical studies [ 49 , 60 ] in this work the ability of SSM to improve the inhibitory role of TQ on human SH-SY5Y neuroblastoma cell migration was explored.…”

Pharmacology, Toxicity, Bioavailability, and Formulation of Magnolol: An Update

“…In vitro release test showed that MG had sustained release behavior after being encapsulated in micelles. The permeability of MG through the Caco-2 cell monolayer was enhanced, and the relative bioavailability of oral MG-M was 2.83 times higher than that of the raw MG (Shen H et al, 2018). It can be seen that the mixed micelle drug delivery system can improve the poor water solubility and bioavailability of MG.…”

“…Mixed Soluplus (SOL) and Solutol HS15 (HS15), SOL, and D-alpha-tocopheryl polyethylene glycol 1,000 succinate (TPGS) were used to prepare MG-loaded mixed micelles (MG-M) MG-H and MG-T, respectively. The relative oral bioavailability of MG-T and MG-H were increased by 2.39-and 2.98-fold, respectively, compared to that of raw MG, indicating that MG-H and MG-T could promote the absorption of MG in the gastrointestinal tract (Ding et al, 2018). Shen et al also prepared MG-M by pluronic F127 and L61, and its drug loading efficiency and entrapment efficiency were 81.57 ± 1.49% and 27.58 ± 0.53%, respectively.…”

“…In recent years, the bioavailability of MG has been significantly improved by various formulations including solid dispersion (Ochiuz et al, 2016;Tang et al, 2016;Stefanache et al, 2017b;Stefanache et al, 2017a;Li et al, 2019), phospholipid complex (Liu et al, 2020), liposome (Chen, 2008;Chen, 2009;Shen et al, 2016), nanoparticles (Wang et al, 2011), emulsion (Sheng et al, 2014), mixed micelles (Shen H et al, 2018;Ding et al, 2018), β-cyclodextrin inclusion compound (Qiu et al, 2016), and Zrbased organometallic framework (Santos et al, 2020) (Table 3).…”

Magnolol and Honokiol: Two Natural Compounds with Similar Chemical Structure but Different Physicochemical and Stability Properties

“…Phosphotungstic acid solution, sodium phosphate monobasic and In addition to the pharmacological actions described above, several preclinical studies have shown that magnolol and honokiol are also effective against different types of cancer such as lung, prostate, breast, gall bladder, colon, skin, and hepatocellular carcinoma [20,21]. However, their potential use in clinical applications is restricted by their very low oral bioavailability [17,22,23] Magnolol and honokiol are commercially available as pure substances isolated from magnolia extracts. In the solid state, both compounds show a high degree of crystallinity, with melting points around 102 • C (magnolol) and 87 • C (honokiol) [24][25][26].…”