Development of gelatin methacrylate (GelMa) hydrogels for versatile intracavitary applications

Abstract

Applicability of hydrogels as drug delivery systems is on the rise due to their highly tunable degree of polymeric crosslinking to attain varying rates of payload release. Sustaining the release of therapeutic payloads at certain physiological sites has been the need of the hour to treat disorders such as peritoneal or pleural malignancies. These disorders can be targeted via intracavitary administration of hydrogels, providing localized therapy. In this study, a gelatin methacrylate (GelMa) hydrogel with tunable physicochemical traits is developed and characterized. A hydrogel-based depot system was curated using GelMa as backbone, a photo-initiator (lithium phenyl-2,4,6-trimethylbenzoylphosphinate) and a chemical crosslinker (N,N-methylenebisacrylamide). Hydrogels were optimized using a 2³ factorial design, by testing for their gelling time, injectability, viscosity change, elasticity, bio-adhesion, swelling-index, in vitro degradation, in vitro release, and biocompatibility. Gelling time for hydrogel formulations was found to be <60 seconds with gelling being achieved in as fast as 24 seconds. Bio-adhesion studies revealed that formulations with higher concentrations of both crosslinkers had more adhesion to guinea pig lung tissues. Hydrogels with higher swelling showcased a more sustained release. Biocompatibility studies for hydrogel formulations was done by evaluating formulation performance in MTT, live/dead, and apoptosis assays performed using non-malignant Human embryonic kidney cells (HEK-293). The optimized hydrogel formulations were biocompatible, yielding >90% cellular viability over 72 hours. This delivery system prototype may be used to deliver potent chemotherapeutics locally, reducing off target effects and improving therapeutic benefits.