Stimuli-Responsive Permeation of Niacin from Gelatin/Polyacrylamide Hybrid Hydrogels under Electric Field and Ultrasound Stimulation

Abstract

To investigate the permeation efficiency of hybrid gelatin (GE)/polyacrylamide (PAM) hydrogel for transdermal drug delivery patch application, niacin (NA) was chosen as a hydrophilic model active pharmaceutical ingredient to evaluate permeation behavior. To investigate the effect of crosslinking ratio on the permeation characteristics, gelatin/polyacrylamide hydrogels were prepared at different crosslinking ratios (Mol_MBAA/Mol_AM at 0.001, 0.005, 0.01, 0.035 for GE_PAM_0.001, GE_PAM_0.005, GE_PAM_0.01 and GE_PAM_0.035). The permeation experiment was conducted at pH 7.4 and a temperature of 37 °C for 24 h with or without external stimuli (electrical potential, ultrasound, and a hybrid system). For passive permeation, the amount of NA permeation increased with time and reached a plateau value. The GE_PAM_0.01 showed the highest NA permeation due to its highest % swelling. To enhance the permeation efficiency, external electrical potential and ultrasound were applied. The amount of NA permeation increased with increasing electrical potential due to electro-repulsive forces. For the ultrasound-assisted system, the NA permeation increased with longer durations of ultrasound application due to thermal effects and micro-pathway generation within the skin membrane. In the hybrid system that combined the electrical potential with ultrasound, the amount of NA permeation reached 78.24%, which was higher than that of either the electrical potential or ultrasound alone. Thus, GE/PAM hydrogel, which was efficient in drug permeation under external stimulation, can be developed to become an NA transdermal patch when being controlled by external electrical potential and ultrasound.