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.