Minoxidil/salicylic acid hydrogel formulated for alopecia treatment: Supramolecular interactions modulate physicochemical properties and biological activities revealed by experimental and theoretical studies

Abstract

Although alopecia does not cause apparent physical discomfort, it can significantly affect the quality of life and mental health of patients. In order to develop a new strategy for alopecia treatment, a supramolecular hydrogel formulation was prepared based on the carbomer matrix and drug salt of minoxidil (MXD) and salicylic acid (SA). The MXD/SA crystalline solid was characterized using X-ray crystallography and X-ray photoelectron spectroscopy. The prepared MXD/SA supramolecular hydrogel was studied by Fourier-transform infrared spectroscopy, thermal analysis, rheological assay, in vitro diffusion and penetration, scanning electron microscope, and molecular dynamics simulations. The experimental and theoretical results reveal that supramolecular interactions can alter the porous network of hydrogels, leading to enhanced thermal stability, transdermal diffusion, and temperature-responsive skin adhesion. Furthermore, the results of in vivo hair growth model and histological analysis indicate that the MXD/SA hydrogel not only accelerates hair growth but also improves hair follicle regeneration ability. Therefore, the MXD/SA hydrogel has the potential for the efficient treatment of alopecia, providing an important pathway to arrange the formulations that can utilize the supramolecular interactions for improved therapeutic efficacy.