Development and comprehensive evaluation of Tetronic® 1304-Labrasol® mixed micelles for lung-targeted drug delivery: A physicochemical, biological, and computational approach for improved pulmonary chemotherapy

Abstract

Lung-targeted drug delivery has emerged as one of the most promising strategies for treating lung cancer, enhancing local drug accumulation while minimizing systemic toxicity. Pulmonary drug delivery is a key focus of nanomedicine, enabling the direct administration of chemotherapeutics to the lungs. Herein, we report the formulation and detailed physicochemical characterization of mixed micelles composed of Tetronic® 1304, a pH- and thermo-responsive block copolymer, and Labrasol®, a nonionic surfactant known for its emulsifying and permeation-enhancing properties.

The phase behavior was evaluated by cloud point (CP) measurements, micellar size and shape by dynamic light scattering (DLS), small-angle neutron scattering (SANS), and relative viscosity by viscosity measurements. The hydrophobic model anticancer drug quercetin (QCT) was encapsulated into mixed micelles, and its increased solubility was confirmed by UV–visible spectroscopy. The in vitro cytotoxicity against lung epithelial adenocarcinoma cells (A549) was studied via an MTT assay, where IC₅₀ values were calculated to define the efficiency of drug-loaded micelles. Moreover, increased intracellular reactive oxygen species (ROS) levels, along with nuclear damage, evidenced that micelles induced both apoptosis and necrosis. These results demonstrated that T1304-Labrasol® mixed micelles are efficient nanocarriers of hydrophobic drugs in pulmonary applications.

DFT-based computational analysis revealed that mixing T1304-Labrasol® induces favorable dipole alignment, enhanced thermodynamic stability, and increased electronic softness, collectively promoting stronger intermolecular interactions and improved self-assembly behaviour. This study provides important insight into their possible applications as nanocarriers in lung-targeted chemotherapy and thus constitutes a contribution to developing more active and targeted nanomedicine-based treatments against lung cancer.

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Materials

Tetronic® 1304 was received as a gift sample from BASF Corp. India. Gattefossé, India, has generously provided a sample of Labrasol®. Both the amphiphiles were of analytical grade with a purity of 98–99 % and did not need any external purification. The anticancer drug, quercetin, was purchased from Sigma-Aldrich with a purity of ≥ 98 % and was used as received. All experimental solutions were prepared using high-purity deionized water from the Millipore Milli-Q system.

Gaurang Dalsaniya, Deep Bhalani, Aakash Shukla, Mayursing Girase, Gitika Kharkwal, Ketan Kuperkar, Sugam Kumar, Vinod K. Aswal, Sadafara A. Pillai, Development and comprehensive evaluation of Tetronic® 1304-Labrasol® mixed micelles for lung-targeted drug delivery: A physicochemical, biological, and computational approach for improved pulmonary chemotherapy, Colloids and Surfaces A: Physicochemical and Engineering Aspects, Volume 737, Part 2, 2026, 139870, ISSN 0927-7757, https://doi.org/10.1016/j.colsurfa.2026.139870.

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