Bovine milk-derived exosomes as nanocarriers for curcumin: Enhancing stability against gastrointestinal digestion and systemic bioavailability

Curcumin, the main polyphenol of Curcuma longa , is a potent antioxidant and anti-inflammatory compound, but its limited solubility and instability largely hamper its therapeutic potential, and high first-pass metabolism - collectively referred to as the “curcumin paradox”. Traditional synthetic nanocarriers, such as liposomes, may not be stable in the gastrointestinal tract and are subject to rapid systemic clearance. In this regard, bovine milk-derived exosomes (BMEs) have emerged as natural nanocarriers with inherent biocompatibility, low immunogenicity, and enhanced stability. BMEs are endowed with a distinctive lipid–protein structure and bioactive molecules such as lactadherin, which promote cellular internalization and gastrointestinal stability. This review explores the critical role of BMEs in enhancing curcumin stability, bioavailability, and systemic delivery. Moreover, drug release profiles are analyzed using well-known mathematical models (Higuchi and Korsmeyer-Peppas equations) to gain insight into the mechanisms of controlled release. Issues associated with large-scale exosome isolation, drug loading, and scale-up are also addressed. Valorization of dairy by-products for exosome extraction represents a step toward circular bioeconomy and underscores the promise of BMEs as a viable and efficient delivery system for functional food and medical uses.