Tunable soy protein isolate hydrogel for nanoparticles brain release

Implantable biomaterials for local drug release have been investigated to avoid the ned to cross the blood-brain barrier, which is one of the major limitations of current brain tumors therapies. However, their translation is still limited by inadequate tissue compatibility and suboptimal drug/nanoparticles release. In this study, soy protein isolate (SPI) hydrogels were engineered using microbial transglutaminase (MTGase) as a safe, naturally derived crosslinker, and optimized for brain-relevant constraints. Hydrogels were prepared at 10% and 12% (w/v) SPI and crosslinked with 20 or 40 mg MTGase/g SPI. Crosslinking was confirmed by SDS-PAGE, while scanning electron microscopy revealed a highly porous, microstructure with well-defined cavities. Hydrogels showed high water content (87-89%) and controlled swelling behavior over 72 h that is inversely correlated to MTGase concentration. Rheological analysis demonstrated solid-like behavior (G' > G''), shear-thinning viscosity suitable for syringe-based injection, and mechanical stability under dynamic stress. Among the tested samples, the 10% (w/v) SPI hydrogel crosslinked with 20 mg MTGase/g SPI exhibited a storage modulus (~260 Pa) closely matching native brain tissue, making it the most suitable candidate for intracranial application. This formulation enabled controlled release of 100-200 nm liposomes and sustained delivery of doxorubicin-loaded liposomes, resulting in a significant reduction in glioblastoma cell viability in vitro. Importantly, the hydrogel showed no cytotoxicity and did not allow cancer cell adhesion and infiltration, confirming its bioinert nature. Overall, MTGase-crosslinked SPI hydrogels emerge as versatile, scalable, and brain-compatible biomaterials for injectable implants and sustained local nanoparticle release.