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<p>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′ &gt; 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.</p> Graphical Abstract <p></p>

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Tunable soy protein isolate hydrogel for nanoparticles brain release

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年5月22日

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  • Matilde Ciprandi,
  • Veronica Fontanini,
  • Patrizia Sommi,
  • Umberto Anselmi-Tamburini,
  • Silvia Sesana,
  • Francesca Re

摘要

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.

Graphical Abstract