# Pulmonary drug delivery of quercetin through scalable PEGylated mixed micelles of Gelucire® and Tetronic®

## TL;DR

This study develops mixed micelles to improve the solubility and effectiveness of quercetin, a lung cancer drug, for better pulmonary drug delivery.

## Contribution

A scalable mixed micellar system using Gelucire® and Tetronic® is developed to enhance quercetin solubilization and cytotoxicity.

## Key findings

- Mixed micelles of Gelucire® and Tetronic® improved quercetin solubilization and cytotoxicity in A549 cells.
- Micellar growth and drug encapsulation increased in saline conditions due to the salting-out effect.
- The mixed system showed intermediate drug release and enhanced ROS generation and DNA damage in cancer cells.

## Abstract

Many potent anticancer agents suffer from poor water solubility, limiting their industrial translation into effective formulations. Although single micellar systems have been explored to address this issue, they often exhibit low stability and encapsulation efficiency. To overcome these limitations, this study developed and characterized PEG-based mixed micelles composed of Gelucire® 48/16 and Tetronic® 1304 (T1304), aiming to improve the solubilization and cytotoxicity of a model lung cancer drug, quercetin (QCT). The micelles were extensively analysed using cloud point (CP), small-angle neutron scattering (SANS), and high-performance liquid chromatography (HPLC) techniques. SANS confirmed that Gelucire® 48/16 formed spherical or ellipsoidal micelles depending on composition with T1304. Micellar growth and improved drug encapsulation are noticed in saline conditions through the salting-out effect. In vitro cytotoxicity studies in lung epithelial adenocarcinoma (A549) cells demonstrated that Gelucire® 48/16 micelles enhanced the cytotoxic effect of QCT, while T1304 provided controlled release, with the mixed system offering intermediate modulation. The results indicate that mixed micellar systems showed a potential cytotoxic effect via increased ROS generation and DNA damage, ultimately damaging cancer cells. Additionally, our findings support a practical and commercially viable approach for enhancing the solubility and therapeutic efficacy of hydrophobic drugs, which can be further useful in various biomedical applications, such as healthcare formulations and drug delivery.

Mechanistic illustration of composition- and salt-driven micellar evolution in Gelucire®-T1304 self-assembled nanostructures.