The Effects of Hydrophobic Antimicrobial Additives on the Stability and Rheology of Thermoresponsive Nanocomposite Hydrogels

ABSTRACT

This study investigates the rheological behavior of a hybrid Laponite + Pluronic F127 (LP + F127) system in the presence of hydrophobic additives, using a series of model hydrophobic antimicrobial agents, parabens, as model compounds. There have been several studies focusing on optimizing the interaction of LP + F127 with various drugs; however, few have considered the aging aspects of Laponite. We aged all samples for 35 days based on dynamic light scattering (DLS) studies, which indicated system stabilization between 31 and 58 days. In our aged system, we observed that the addition of parabens significantly increased both storage and loss moduli, indicating more solid‐like behavior, especially at lower temperatures. Among the parabens, propyl paraben produced the stiffest gels, followed by ethyl and then methyl paraben. We also found that increasing the concentration of parabens from 0.25 wt.% to 0.5 wt.% increased gel stiffness, showing concentration‐dependent tunability. In the 0.25 wt.% methyl and ethyl paraben samples, the critical gelation temperature decreased by 9°C relative to samples without paraben, suggesting the addition of these parabens shifted gelation to lower temperatures. In the 0.50 wt.% propyl paraben samples, rheology data indicated that the samples were already gel‐like at the start of measurements, suggesting that the increased paraben concentration shifts the system to a gel state earlier in time, possibly during the 35‐day aging period. Drug release experiments were performed to compare the release rates of model drugs from our aged LP + F127 system, and the gels were found to significantly slow down drug diffusion. Our results align with previous findings with hydrophobic additives in micelle systems but suggest that the combined effect of aging, micelle structure, and additive interactions point to a complex but useful system for drug delivery applications in physiological environments.