Skin Permeation of Hydrophilic Middle-to-High Molecular Weight Model Drugs from Decanoic Acid/Arginine Supramolecular Hydrogels

Abstract

Decanoic acid/arginine supramolecular hydrogels (C10/Arg) were prepared and evaluated for use as skin-application formulations to improve the skin permeation of hydrophilic middle-to-high-molecular-weight drugs. Dextran (Mw; 6000 Da [Dex]) was used to evaluate the physicochemical properties of the hydrogels, and fluorescein isothiocyanate-Dex (Mw; 4000 Da [FD4], Mw; 40000 Da [FD40]) was used as a model drug to evaluate skin permeability. The addition of 1% Dex to C10/Arg resulted in a translucent supramolecular hydrogel with a lamellar liquid crystal structure, and the addition of a low-molecular-weight model drug to this hydrogel did not significantly affect its physicochemical properties. However, the addition of middle-molecular-weight Dex (6000 Da) changed the rheological properties of the gel, strengthening its internal structure and increasing its elasticity. In vitro skin permeation experiments of model drugs released from C10/Arg gels were performed using Yucatan micropig skin. C10/Arg increased the cumulative amount of FD4 permeation by 40 times after 24 h compared to the application of aqueous FD4 solution. No skin permeation from the aqueous FD40 solution was observed, but permeation was observed following treatment of the skin sample with C10/Arg. The enhanced skin permeation of model drugs by hydrogels was largely due to the contribution of C10 in the hydrogels.