Enhanced oral bioavailability of magnolol via mixed micelles and nanosuspensions based on Soluplus ^® -Poloxamer 188

Abstract

Magnolol, known to have extensive biological activities, is the major bioactive ingredient isolated from the root and stem bark of Magnolia officinalis. However, the clinical application of magnolol is limited by poor aqueous solubility and absorption. The aim of this study is to develop novel mixed micelles and nanosuspensions composed of two biocompatible copolymers, Soluplus V R and Poloxamer 188, and to improve the solubility and oral bioavailability of magnolol. The magnolol-loaded mixed micelles (MMs) and magnolol nanosuspensions (MNs) were prepared to use film hydration and antisolvent methods, respectively. The optimal MMs and MNs formulations were prepared to use magnolol, Soluplus V R , and Poloxamer 188 in ratios of 1:12:5 and 2:1:1, respectively. The average particle size of MMs was 111.8 ± 14.6, and MNs was 78.53 ± 5.4 nm. The entrapment and drug loading efficiency for MMs were 89.58 ± 2.54% and 5.46 ± 0.65%, correspondingly. The drug loading efficiency of MNs was 42.50 ± 1.57%. In the in vitro release study, MMs showed a slow drug release while that of MNs was fast. The results of the Caco-2 transcellular transport study indicated that both MMs and MNs increased the permeation of magnolol. MMs and MNs markedly promoted gastrointestinal drug absorption by 2.85 and 2.27-fold, respectively, as shown in the pharmacokinetics study. These results indicated that both MMs and MNs formulations prepared with Soluplus V R and Poloxamer 188 are promising drug delivery systems for improving the oral absorption of insoluble drugs in the gastrointestinal tract.

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

“…MG (5 μM) significantly inhibited trimethyltin (TMT)-mediated neuronal death and microglial activation by inhibiting ROS production and the activation of JNK, p38 MAPKs, and NF-κB in HT22 cells and BV-2 cells ( Kim and Kim, 2016 ). Both MG (12.5 μM) and honokiol (6.25 μM) showed effective behavioral and electrophysiological antiepileptic activities in pentylenetetrazole and ethyl ketopentenoate models ( Li G et al, 2020 ).…”

Pterostilbene-Loaded Soluplus/Poloxamer 188 Mixed Micelles for Protection against Acetaminophen-Induced Acute Liver Injury

“…Poloxamer 188 consists of two polyethylene oxide chains separated by a polypropylene oxide chain. These two materials are commonly used to construct drug delivery systems . In this study, we prepared Soluplus/poloxamer 188 MMs for the delivery of PTE.…”

“…It is an amphiphilic copolymer that self-assembles in solution to form micelles with a low critical micelle concentration (CMC) . Poloxamer 188 has been recognized by the Food and Drug Administration as a pharmaceutical excipient with excellent safety and is often used as a nano-delivery vehicle . However, the disadvantages of micelles prepared with poloxamer 188 alone, such as poor drug-carrying capacity and low stability, limit further applications.…”

Computational and Experimental Assessments of Magnolol as a Neuroprotective Agent and Utilization of UiO-66(Zr) as Its Drug Delivery System

“…Despite the diverse pharmacological effect reported for magnolol, the bioavailability of magnolol is low (4.9%) mainly due to its poor water solubility, which also impedes its absorption. , Among the promising approaches to shuttle neuroactive compounds across the blood-brain barrier (BBB) is through the development of novel drug delivery systems . Highly porous inorganic materials such metal–organic frameworks (MOFs) are considered candidates for the delivery of different drugs with advantages of ease in preparation and formulation via encapsulation, controlled release, and improved organ targeting .…”