Cloudberry-derived nanovesicles as stable oral drug delivery systems: gastrointestinal stability and age-related biodistribution in mice

Plant-derived nanovesicles (PDNVs) have emerged as promising candidates for oral drug delivery due to their natural biocompatibility and ability to transport bioactive molecules. However, their stability within the gastrointestinal (GI) tract and efficacy in aging populations remain largely unexplored. In this study, we isolated nanovesicles from cloudberries (Rubus chamaemorus), which are rich in bioactive polyphenols, to evaluate their potential as stable oral drug delivery vehicles. We characterized the physical properties and RNA content of these cloudberry-derived nanovesicles (CNVs) and investigated their stability under simulated GI conditions in vitro. The CNVs maintained their structural integrity and functional properties after exposure to harsh digestive conditions, demonstrating resilience against digestive enzymes and pH variations. Using Caco-2 cell monolayers, we confirmed efficient cellular uptake and trans-epithelial transport of CNVs without inducing cytotoxic effects. Furthermore, we assessed the biodistribution and immune responses to CNVs in both young and elderly mice. In vivo imaging revealed favorable biodistribution patterns, prolonged retention in the GI tract, effective intestinal absorption, transfer to the bloodstream, and low immunogenicity in both age groups. Notably, aging influenced the biodistribution of CNVs, with elderly mice exhibiting delayed gastric emptying and prolonged GI retention, likely due to age-related physiological changes. These findings suggest that CNVs are promising, stable, and biocompatible oral drug delivery systems suitable for both young and elderly populations, highlighting their potential for therapeutic applications, especially in age-related conditions.