Tuning Supramolecular Hydrogels with Surfactant‐Based Organic Nanoparticles for Drug Delivery

Supramolecular hydrogels derived from the self-assembly of low molecular weight gelators, especially those derived from amino acids and peptides, are gaining increasing attention in drug delivery because of their stimuli responsive behavior. This study explores the influence of surfactant-based nanoparticles-CTAB (cationic), SDS (anionic), and TX100 (nonionic), at various concentrations such as below, at, and above their respective critical micelle concentrations (CMC), as internal stimuli in modulating the self-assembly, mechanical properties, thermal stability, and functional behavior of Fmoc-Phe hydrogels for the control release of chemotherapeutic drug daunorubicin utilized in skin cancer treatment. CTAB micelles accelerate gelation and enhance fibrillar density, mechanical strength, and thermal stability by neutralizing the anionic carboxylate groups of Fmoc-Phe. In contrast, SDS impedes gelation and disrupts fibrillar networks due to electrostatic repulsion, especially at concentrations above CMC. TX100, through hydrophobic interactions, subtly alters fibril morphology without significantly disturbing hydrogen bonding. Microscopic and spectroscopic analyses reveal distinct interaction mechanisms for each surfactant, which subsequently alters the release profiles. These findings demonstrate that surfactant nanoparticles offer a tunable strategy to control the physicochemical and functional properties of Fmoc-Phe hydrogels, positioning them as promising candidates for biomedical applications such as drug delivery, tissue engineering, and injectable therapies.