Cholate-modified polymer-lipid hybrid nanoparticles for oral delivery of quercetin to potentiate the antileukemic effect

Abstract

Background:

Quercetin (QUE) shows a potential antileukemic activity, but possesses poor solubility and low bioavailability.

Purpose:

This article explored the bile salt transport pathway for oral deliver of QUE using cholate-modified polymer-lipid hybrid nanoparticles (cPLNs) aiming to enhance its antileukemic effect.

Methods:

QUE-loaded cPLNs (QUE-cPLNs) were developed through a nanoprecipitation technique and characterized by particle size, entrapment efficiency (EE), microscopic morphology and in vitro drug release. In vitro cellular uptake and cytotoxicity of QUE-cPLNs were examined on Caco-2 and P388 cells; in vivo pharmacokinetics and antileukemic effect were evaluated using Sprague Dawley rats and leukemic model mice, respectively.

Results:

The prepared QUE-cPLNs possessed a particle size of 110 nm around with an EE of 96.22%. QUE-cPLNs resulted in significantly enhanced bioavailability of QUE, up to 375.12% relative to the formulation of suspensions. In addition, QUE-cPLNs exhibited excellent cellular uptake and internalization capability compared to cholate-free QUE-PLNs. The in vitro cytotoxic and in vivo antileukemic effects of QUE-cPLNs were also signally superior to free QUE and QUE-PLNs.

Conclusion:

These findings indicate that cPLNs are a promising nanocarrier able to improve the oral bioavailability and therapeutic index of QUE.

Keywords:

• quercetin
• polymer-lipid hybrid nanoparticles
• bile salt
• bioavailability
• leukemia

Acknowledgments

This work is supported by the Key Research Project of Henan Provincial Science and Technology Department (No. 112102310306), and the authors thank the Department of Pharmaceutics of Huaihe Hospital Affiliated to Henan University for financial assistance.

Disclosure

The authors report no conflicts of interest in this work.