# Developing and Applying a Single Strategy for Improved Intestinal Permeability of Diverse and Complex Phytomolecules: Nanoformulations of Rutin, Quercetin, Thymoquinone Provide Proof-of-Concept

## TL;DR

This paper introduces a simple method to improve the intestinal absorption of poorly soluble plant-based compounds using nanoparticles, showing better performance for rutin, quercetin, and thymoquinone.

## Contribution

A single, easy-to-apply strategy using Eudragit-based nanoparticles to enhance intestinal permeability of diverse phytomolecules is proposed and validated.

## Key findings

- Nanoparticles of rutin, quercetin, and thymoquinone showed significantly higher intestinal permeability compared to their free forms.
- The developed nanoparticles followed Higuchi kinetics with non-Fickian diffusion mechanisms.
- The apparent permeability of phytomolecule-loaded nanoparticles was significantly greater than the native compounds.

## Abstract

The clinical use and efficacy of phytomolecules are often hampered as their complex structure, poor aqueous solubility and low biological stability restricts their intestinal permeability which results in low oral bioavailability. Rutin (RT), quercetin (QU), thymoquinone (TQ) are few of such potent and therapeutically versatile phytomolecules that await maximal utilization. To address this lacuna, an attempt was made to develop a single strategy for enhanced intestinal permeation that can be applied to diverse phytomolecules.

A simple idea with easy-to-apply method was developed that involved preparing nanoparticles of the phytomolecules RT, QU, TQ using Eudragit matrix (RT-PNP, QU-PNP, TQ-PNP) and examined for particle characteristics, EE, in vitro release and kinetics. Phytomolecule loaded nanoparticle (PNPs) were encapsulated in HPMC grade capsule shell and evaluated for intestinal permeability by everted gut sac method.

The average particle sizes of RT-PNP, QU-PNP, TQ-PNP were 446±0.152, 39.6±0.006 and 186±0.513 nm, polydispersity indices were<0.5 with negative zeta potential. The % release of respective phytomolecule from RT-PNP, QU-PNP, TQ-PNP was significantly higher (P<0.05) at pH 6.8 than pH 1.2. PNPs followed Higuchi kinetics with non-Fickian diffusion mechanisms. The apparent intestinal permeability (Papp) of RT-PNP, QU-PNP, TQ-PNP were 14.45±4.85, 12.96±1.73 and 30.87±8.75 µg/cm2, respectively, significantly (<0.5) greater vs RT, QU, TQ, respectively. CLSM confirmed significantly higher (P<0.05) intestinal permeation of RT-PNP, QU-PNP, TQ-PNP vs RT, QU, TQ, respectively.

Developed PNPs appear to be a good approach to increase the permeability of hydrophobic phytomolecules.