Developing Metal-Polyphenol Network-Based Single-Protein Particle Encapsulation System for Sustained Release of Whey Protein to Mitigate Sarcopenia.

Sarcopenia has emerged as a major health challenge in the aging population. Whey protein (WP)-rich in branched-chain amino acids-is an important nutritional supplement for mitigating sarcopenia. However, the rapid digestion of WP limits its therapeutic efficacy. Developing a sustained-release system for WP may enhance its effectiveness in mitigating sarcopenia. Herein, a novel "single-protein particle encapsulation" (SPPE) system is developed to protect WP and control its release. Specifically, the "molecular glue" metal-polyphenol networks (MPNs) are assembled onto the surface of individual polymerized WP isolate (PWPI) particles as an intermediate layer and bridged with the saccharide hyaluronic acid (HA) to construct PWPI@MPNs/HA. The results showed that PWPI@MPNs/HA precisely regulates the release rate of PWPI in the gastrointestinal tract. In a murine sarcopenia model, PWPI@MPNs25/HA significantly improves lean body content, grip strength, grid hanging time, exhaustion time, and exhaustion distance. The underlying molecular mechanism involves activation of the PI3K/AKT/mTOR signaling pathway and suppression of the muscle atrophy factors MuRF-1 and Atrogin-1 in the ubiquitin-proteasome system via PWPI@MPNs/HA. The SPPE system developed in this study may have broad future applications in protein protection and delivery.