[Development of Novel Supramolecular Gels for Pharmaceutical Applications and Mechanistic Elucidation of Supramolecular Gelation].

Supramolecular gels are soft materials formed through the self-assembly of low-molecular-weight gelators via noncovalent interactions. Because their molecular structures can be precisely designed, supramolecular gels are promising functional materials with stimuli-responsive properties. This review summarizes our studies on the design and development of supramolecular gels for pharmaceutical applications, as well as the mechanistic elucidation of supramolecular gelation. First, disaccharide-coupled amphiphilic ureas were designed as low-molecular-weight gelators for small intestine-targeted drug delivery systems. Maltose- and lactose-coupled amphiphilic ureas, Mal-Cn and Lac-Cn, were synthesized in three steps. The resulting supramolecular gels showed enzymatic hydrolysis-responsive phase transitions triggered by disaccharidases. In particular, the supramolecular gel formed from Lac-C8 was degraded by β-galactosidase, and the entrapped model drug, Rhodamine 6G, was released as the gel degraded. These results demonstrate the potential of enzymatic hydrolysis-responsive supramolecular gels as drug carriers. Second, the gelation mechanism of a urea-based low-molecular-weight gelator was investigated using high-speed atomic force microscopy. Direct observation revealed that gel-forming fibers grew through repeated elongation and pause phases. A block-stacking model was proposed to explain the intermittent growth of fibers. Through these observations and additional experimental analyses, we elucidated the mechanism of supramolecular gelation.