HIFU-triggered burst release of gallic acid from gelatin/polyvinyl pyrrolidone hydrogel network crosslinked with magnesium gallate MOF

In this study, we report the high-intensity focused ultrasound-triggered burst release of gallic acid from a gelatin-polyvinyl pyrrolidone (PVP) based hydrogel crosslinked with magnesium gallate (Mg-Gal) microparticles. Hydrogel was fabricated with 5% gelatin and 5% PVP as polymeric components crosslinked with 0.5% of Mg-Gal microparticles as crosslinker. Following physico-chemical characterization of the hydrogel, gallic acid release pattern was studied at different pH and temperature. In vitro biocompatibility & anti-cancer potential of microparticles and hydrogels were established. Further, high-intensity focused ultrasound (HIFU) induced drug release and enhanced bioactivity were also demonstrated. Fabricated hydrogels were characterized to show strong crosslinking network reinforced by ionic interactions. Mechanical and hydration properties correlated with release kinetics of gallic acid signifying the pH & temperature responsiveness of the hydrogel. PG-Mg-Gal showed excellent biocompatibility with dermal fibroblast (<10%) and inhibited the proliferation & migration of 4T1 cells. HIFU triggered the rapid release of gallic acid from PG-Mg-Gal, where the release rate was consistent for 30 min (30%) and up to 60% release was achieved at 90 mins. The drug release process showed consistently significant release rate compared to the untreated control. Enhanced bioactivity (20%; > 5 times of untreated hydrogel) of PG-Mg-Gal followed by burst release of gallic acid through HIFU treatment was demonstrated after 4 hrs using Live/Dead cells staining. In conclusion, HIFU-triggered delivery of gallic acid from PG-Mg-Gal showed great potential as a biocompatible and rapid delivery system which enhances the cytotoxic potential of Mg-Gal formulation through delivery at the targeted site.