Food-derived β-lactoglobulin nanofibrils: An efficacy, safe, and scalable solution to overcome oral insulin delivery challenges.

ABSTRACT: Oral delivery of biologics presents a formidable challenge: achieving high bioavailability without compromising gastrointestinal barrier integrity or clinical scalability-a trilemma that remains unaddressed by existing chemical permeation enhancers, ligand-modified nanoparticles, or exosome platforms. Here, we repurpose β-lactoglobulin (BLG) nanofibrils that resolve this challenge through a unique "enhance-degrade-restore" mechanism. In vivo, these nanofibrils enable oral insulin bioavailability reaching 10.2-12.3 %, and long-term safety studies confirm the absence of intestinal damage. Mechanistic studies reveal that the nanofibrils facilitate Ca²⁺ influx-induced calpain activation to enhance paracellular permeability, followed by protease-mediated degradation that ensures time

SUBMITTER: Liu X 

PROVIDER: S-EPMC12686822 | biostudies-literature | 2026 Mar

REPOSITORIES: biostudies-literature