Work

Exploring glutathione-decorated micelles for drug delivery: A promise for enhanced cellular uptake

Year: 2025

Type: article

Abstract: This study aimed to evaluate the effect of thiolated micelles on the cellular uptake of their payload. Reduced and oxidized glutathione were covalently attached to palmitic acid via amide bond formation. Micelles formed with these thiolated surfactants (M P-GSH and M P-GSSG-P ) were evaluated regarding critical micellar concentration (CMC) and hemolytic activity. Cytotoxicity was evaluated on HEK 293 and HeLa cells. Diffusion of micelles in these cells was evaluated by fluorescence correlation spectroscopy (FCS). Furthermore, cellular uptake of micelles containing coumarin-6 as model drug was analyzed by flow cytometry and confocal laser scanning microscopy. CMC of M P-GSSG-P , M P-GSH , and palmitic acid micelles (M PA ) was determined to be 0.455 mM, 0.166 mM, and 0.046 mM, respectively. At a concentration of 0.5 % M P-GSSG-P, M P-GSH , and M PA caused around 80 % hemolysis. In HEK cells, M P-GSSG-P exhibited toxicity at a concentration of 0.25 %, while M P-GSH showed toxicity at 0.06 % after 4 hours of incubation. In contrast, HeLa cells were more resilient, with only M P-GSH showing toxicity at 0.25 %. Diffusivity of M P-GSH and M P-GSSG-P within the cells was higher than that of M PA . Cellular uptake studies demonstrated a significantly (p < 0.05) enhanced internalization of M P-GSH and M P-GSSG-P , that was 112-fold and 270-fold higher in HEK 293 cells and 12-fold and 60-fold higher in HeLa cells when compared to M PA . These findings suggest that M P-GSH and M P-GSSG-P could serve as promising vehicles for enhancing cellular uptake of drugs. • Palmitic acid conjugates with oxidized glutathione (M P-GSSG-P ) exhibited low toxicity, indicating potential for safe drug delivery. • M P-GSSG-P showed 20-fold faster diffusion time in HeLa cells than palmitic acid micelles (M PA ). • M P-GSSG-P demonstrated 60- and 270-fold higher uptake in HeLa and HEK 293 cells than M PA .

Source: Colloids and Surfaces B Biointerfaces

DOI: 10.1016/j.colsurfb.2025.114664