Lipase-Responsive Nonionic-Amphiphilic Nanocarriers for Biomedical Applications

Amphiphilic architectures derived from biocompatible and biodegradable materials have garnered considerable attention owing to their significant therapeutic potential in the biomedical field. In an aqueous environment, these systems exhibit diverse self-assembly behavior, leading to the formation of nanostructures with varied morphologies. Typically, such nanostructures consist of a hydrophilic corona surrounding a hydrophobic core that serves as a nanoscale reservoir for lipophilic guests, thereby conferring effective nanocarrier functionality to the amphiphilic system. Motivated by these characteristics, we synthesized a series of four nonionic-amphiphilic compounds by conjugating monomethoxypolyethylene glycol (mPEG) as the hydrophilic moiety and an alkyl chain as the hydrophobic segment onto a central 3-hydroxy-2-(hydroxymethyl)-2-methylpropanoic acid scaffold. The self-assembly behavior of the resulting amphiphiles was investigated by using fluorescence spectroscopy and dynamic light scattering, revealing the formation of small-sized aggregates with hydrodynamic diameters in the range of 7–8 nm. These amphiphiles demonstrated moderate encapsulation capability toward hydrophobic guests, including the fluorescent probe Nile red and the model drug nimodipine. Furthermore, the stimulus-responsive nature of these systems, attributed to the presence of hydrolytically labile ester linkages, was evaluated through lipase-mediated release studies, which confirmed the controlled enzymatic release of the encapsulated cargo.