Milk Exosome-Based Delivery System for Probiotic Encapsulation That Enhances the Gastrointestinal Resistance and Adhesion of Probiotics

The oral administration of probiotics is a promising strategy to regulate the host-intestinal flora balance and improve health. Nevertheless, adverse gastrointestinal (GI) conditions affect the activity of free native probiotics. In this study, a novel probiotic encapsulation system based on milk exosomes (mExos) and DSPE-PEG-PBA was developed. mExos acted as a shield to protect probiotics from harsh GI environments, and DSPE-PEG-PBA served as a bridge between mExos and probiotics. The coated probiotics were characterized by transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), and intrinsic fluorescence spectra. The results showed three probiotics (<i>Akkermansia muciniphila</i> (AKK), <i>Bifidobacterium animalis</i> subsp. <i>lactis</i> BB-12 (BB12), and <i>Lactiplantibacillus plantarum</i> Q7 (Q7)) were coated with mExos@DSPE-PEG-PBA, with encapsulation rates of 90.37 ± 0.45%, 84.47 ± 1.22%, and 70.93 ± 2.39%, respectively. This encapsulation not only preserved the growth activity of the probiotics but also provided robust protection against the detrimental effects of acidic pH, bile salts, and digestive enzymes. The encapsulated strains Q7, BB12, and AKK demonstrated survival rates of 80.99 ± 0.41%, 85.28 ± 0.20%, and 94.53 ± 0.26%, respectively, in an in vitro simulated GI environment. The mExos@DSPE-PEG-PBA-encapsulated probiotics exhibited enhanced hydrophobicity and auto-aggregation capacity, accompanied by a significant improvement in mucoadhesive properties, which collectively potentiated their colonization potential within the gastrointestinal tract. These findings substantiate the potential of mExos as an encapsulation platform for probiotics, providing valuable insights into the selection of exosomes as encapsulating agents to enhance probiotic viability and mucoadhesive capacity.