Intestinal-targeted nanotubes-in-microgels composite carriers for capsaicin delivery and their effect for alleviation of Salmonella induced enteritis

Salmonella is a word-wide food-borne pathogen, which can cause severe enteritis and intestinal microbiota imbalance. Capsaicin (Cap), a food-based bioactive ingredient, has antibacterial and anti-inflammatory properties. However, its low solubility, low bioavailability and the irritation to digestive tract greatly limit its applications. Here, an intestinal responsively “nanotubes-in-microgel” composite carrier was constructed by capturing α-lactalbumin (α-lac) nanotubes in low-methoxy pectin microgels (LMP-NT) (52 μm). Cap was loaded in such system via hydrophobic interaction with a loading capacity of 38.02 mg/g. The LMP microgels remained stable and protected NT/Cap from early releasing in the gastric condition. It showed an excellent mucoadhesive capacity, which can prolong the intestinal retention up to 12 h and control release NT/Cap in intestine. Afterward, NT/Cap could penetrate across the mucus layer deeply and enter the intestinal villi epithelial cells efficiently. LMP-NT microgels achieved a mucoadhesive-to-penetrating transition in response to intestinal pH, improving the epithelium absorption and the in vivo bioavailability of Cap. Oral administration of LMP-NT/Cap could effectively alleviate enteritis caused by Salmonella infection and maintain the homeostasis of gut microbiota. Overall, this work suggested that LMP-NT composite microgels were promising for intestine-targeted and oral delivery of hydrophobic bioactive food compounds.