Resveratrol Supported on Magnesium DiHydroxide (Resv@MDH) Represents an Oral Formulation of Resveratrol With Better Gastric Absorption and Bioavailability Respect to Pure Resveratrol

Abstract

Resveratrol attracts great interest because of the plethora of in vitro effects at the micromolar concentration range. Unfortunately, these effects are difficult to establish in vivo, due to the low concentration of resveratrol reached. This discrepancy is due to the molecules low solubility in water that favors the propensity for an intestinal absorption rather than in the gastric compartment. To address these challenges, we developed a Solid Dispersion of Resveratrol Supported by Magnesium Di Hydroxide formulation (Resv@MDH). This formulation displays increased water solubility and better bioavailability relative to pure resveratrol in the rabbit animal model. In our study, we evaluated the pharmacokinetics profile of resveratrol in six healthy human subjects following 180 mg of oral resveratrol administration, derived from Resv@MDH or pure resveratrol. Free resveratrol was evaluated in the whole blood sample by using HPLC - MS/MS. In comparison with pure resveratrol that displays an increase of the maximum plasma concentration, Cmax at about 90 min and 2 μM, Resv@MDH displays an earlier peak of resveratrol concentration with an increase of Cmax at about 30 min and 6 μM. The different kinetics suggest a main gastric route for resveratrol absorption from Resv@MDH, where, because of its improved dissolution rate, there seems to be a higher propensity for an acidic environment, as opposed to that with pure resveratrol. This conclusion is also supported by the numerical simulation analysis, which considers the principal steps during the oral route administration. Moreover, there is a 2-fold increase in the amount of free resveratrol with respect to pure resveratrol confirming a better bioavailability observed in the animal model. The characteristic feature of the pharmacokinetic profile of Resv@MDH implies that the beneficial properties of resveratrol in human health should be capitalized on it.

Inhibition of Resveratrol Analogs on Human and Rat 3β-Hydroxysteroid Dehydrogenases: Structure–Activity Relationship and Docking Analysis

“…A human study showed that oral administration of RSV in one dose (180 mg/kg) can have a maximum concentration of about 2 μM. 37 However, administration of a RSV−magnesium dihydroxide formulation can have a maximum concentration of about 6 μM. 37 These concentrations may not be enough to achieve the 50% of inhibition on human 3β-HSD1.…”

“…The bioavailability of RSV is relatively low, meaning that only a small proportion of the compound is absorbed into the bloodstream after ingestion. A human study showed that oral administration of RSV in one dose (180 mg/kg) can have a maximum concentration of about 2 μM . However, administration of a RSV–magnesium dihydroxide formulation can have a maximum concentration of about 6 μM .…”

Traditional Chinese medicine monomers: Targeting pulmonary artery smooth muscle cells proliferation to treat pulmonary hypertension

“…The effective concentration of it in serum is only trace levels [ 33 ]. Therefore, a lot of teams are committed to developing new dosage forms, such as melt extrusion method for the high melting point of insoluble resveratrol slow-release solid dispersions, resveratrol with two magnesium hydroxide as the carrier (Resv @ MDH), resveratrol phospholipid complex self-microemulsion drug delivery system, etc., which significantly improve the solubility and bioavailability of resveratrol [ [34] , [35] , [36] ]. Additionally, Li et al [ 37 ] confirmed that dipalmitoylphosphatidylcholine-coated lipid nanoparticles (DPPC-LNs) as inhalable carriers could accumulate resveratrol in pulmonary vessels, which inhibited 5-hydroxytryptamine (5-HT)-induced proliferation of PASMCs, and 25–200 μM Res-DPPC-LNs had no effect on their viability.…”

Caloric restriction-mimetics for the reduction of heart failure risk in aging heart: with consideration of gender-related differences

“…The bioavailability of resveratrol is not reported in these studies but could be a potential reason attributable to the conflicting results. In general, oral resveratrol has low bioavailability but high absorption, due to a rapid hepatic first-pass metabolism [ 173 ]. Of note, the bioavailability of resveratrol can be greatly enhanced over 10 times by piperine, which is a type of bioactive alkaloid [ 174 ].…”