Investigating nanoformulations for the oral delivery of resveratrol to inhibit first-pass metabolism and enhance drug bioavailability

Hassanpour, Akram; Sabzevari, Omid; Kiani Dehkordi, Banafsheh; Amani, Amir; Esmaeili, Fariba; Kharrazi, Sharmin

doi:10.22038/nmj.2026.92596.2345

Investigating nanoformulations for the oral delivery of resveratrol to inhibit first-pass metabolism and enhance drug bioavailability

Document Type : Research Paper

Authors

Akram Hassanpour ¹

Omid Sabzevari ²

Banafsheh Kiani Dehkordi ³

Amir Amani ⁴

Fariba Esmaeili ¹

Sharmin Kharrazi ¹

¹ Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran

² Department of Toxicology and Pharmacology, Faculty of Pharmacy, and Toxicology & Poisoning Research Center, Tehran University of Medical Sciences, Tehran, Iran

³ Department of Pharmaceutics, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran

⁴ Natural Products and Medicinal Plants Research Center, North Khorasan University of Medical Sciences, Bojnurd, Iran

10.22038/nmj.2026.92596.2345

Abstract

Objective(s): Poor oral bioavailability remains a major barrier for the development of many therapeutic agents, underscoring the need for advanced delivery systems. This study aimed to design and evaluate novel nanoformulations of resveratrol (RSV) to improve its absorption and investigate their effects on CYP3A4 inhibition in rats and enhancing simvastatin bioavailability.
Materials and Methods: An oil-in-water nanoemulsion incorporating RSV were synthesized in the oil phase (NE-RSV) and resveratrol-coated gold nanoparticles as a water-soluble form (GNP-RSV). Accordingly, a combined formulation (NE-RSV + GNP-RSV) with maximum RSV loading was prepared and physicochemically characterized. Particle size was measured using Dynamic Light Scattering, and cytotoxicity was assessed on Caco-2 cells via MTT assay. Transport studies across Caco-2 monolayers were performed to examine P-glycoprotein (P-gp) inhibition. Protein expression of CYP3A was assessed through Western blot analysis within liver microsomal preparations. Simvastatin bioavailability in rats was quantified using HPLC following 7-day oral administration. Hematological and biochemical safety markers were also analyzed.
Results: Mean particle sizes were 11.3 ± 6.8 nm for NE-RSV, 22.7 ± 14.3 nm for GNP-RSV, and 36.4 ± 23.0 nm for the combined system. Cytotoxicity results showed no significant reduction in cell viability. Permeability assays confirmed P-gp inhibition. The combined formulation increased simvastatin AUC₀–₂₄ by 2.7-fold and Cmax by 3.05-fold versus controls, with no adverse changes in blood parameters or liver enzymes at 300 mg/kg.
Conclusion: Nanoformulation of resveratrol led to a measurable increase in oral exposure, supporting its applicability for improving absorption of compounds with solubility-limited bioavailability.

Keywords

CYP3A

Resveratrol

Nanoemulsion

Pharmacokinetic

Oral delivery

Subjects

Drug delivery

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