Direct assembly of sodium deoxycholate-ferulic acid hydrogels for enhanced transdermal permeation and long-lasting free radical scavenging activity of bioactive ferulic acid.

Ferulic acid (FA), a natural bioactive compound, faces severe limitations in health-promoting applications due to its poor water solubility and low bioavailability. Different from physical encapsulation of FA in hydrogels, this study develops sodium deoxycholate (NaDC)-FA supramolecular hydrogels through direct assembly of NaDC with FA. The prepared NaDC-FA hydrogels contain 20-80 mM FA, which are about 5-20 times FA amount in the saturated solution. Experimental studies of phase behavior, scanning electron microscopy, small-angle X-ray diffraction, fourier transform infrared and Raman spectra, together with computational simulation reveal that as FA concentration increases from 20 mM to 30 mM, the flexible nanofibers are gradually assembled into homogeneous hydrogel networks via the hydrophobic interaction and hydrogen bonding. Above 30 mM FA, high amount of FA promotes the formation of more rigid and densely packed networks in NaDC-FA hydrogels, where excessive FA-FA interactions disrupt the structural homogeneity of the hydrogels. The different microstructures of NaDC-FA hydrogels contribute to the appearance, melting temperature, and viscoelastic properties of the hydrogels as well as the transdermal permeation behavior of FA. The porcine skin permeation measurement suggests that the cumulative permeation amount of FA in NaDC-FA hydrogels with 50 mM FA is 7.1-fold relative to a saturated FA solution, indicating that the co-permeation of NaDC can reduce the free energy barrier for the transdermal permeation of FA. Moreover, bioactive FA loaded in NaDC-FA hydrogels achieves superior long-lasting free radical scavenging activity owing to the confined microenvironment of fibrous hydrogel networks.