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

## TL;DR

A hydrogel crosslinked with magnesium gallate can release gallic acid on demand using high-intensity focused ultrasound, improving its cancer-fighting potential.

## Contribution

A novel hydrogel system using magnesium gallate as both crosslinker and drug carrier enables HIFU-triggered burst release of gallic acid.

## Key findings

- HIFU triggered rapid and consistent release of gallic acid from the hydrogel over 90 minutes.
- The hydrogel showed enhanced cytotoxicity against cancer cells after HIFU-induced drug release.
- The system demonstrated excellent biocompatibility with dermal fibroblast cells.

## Abstract

•Magnesium gallate acts as drug carrier and crosslinker for gelatin/PVP hydrogel.•Physicochemical and mechanical characteristics of the hydrogel were demonstrated.•Hydrogel responded to HIFU and exhibited burst and on-demand release of gallic acid.•HIFU-triggered gallic acid release resulted in enhanced and rapid cytotoxicity.

Magnesium gallate acts as drug carrier and crosslinker for gelatin/PVP hydrogel.

Physicochemical and mechanical characteristics of the hydrogel were demonstrated.

Hydrogel responded to HIFU and exhibited burst and on-demand release of gallic acid.

HIFU-triggered gallic acid release resulted in enhanced and rapid cytotoxicity.

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.