Gastrointestinal Microenvironment Responsive Nanoencapsulation of Probiotics and Drugs for Synergistic Therapy of Intestinal Diseases.

Abstract

The gut microbiota are prominent in preserving intestinal environmental homeostasis and managing human health, and their dysbiosis has been directly related to many kinds of intestinal diseases. Probiotics-based therapy appears as a promising approach for the treatment of gut microbiota dysbiosis, while it always suffers from limited bioavailability and therapeutic effect after oral administration. Herein, we presented a facile and safe strategy to treat colitis by nanoencapsulation of probiotics and an anti-inflammatory agent, 5-aminosalicylic acid (5-ASA), within the gastrointestinal microenvironment responsive alginate polysaccharide. Because of acid resistance, the alginate-based coating protected probiotics from the harsh gastric condition. The coating could be disintegrated to release probiotics and 5-ASA upon arriving in the intestinal tract, where the pH is normally higher than 5. In the dextran sulfate sodium-induced colitis mouse model, probiotics recovered their bioactivities and acted together with anti-inflammatory 5-ASA to alleviate colitis by upregulating microbiota richness and diversity, reducing expression of proinflammatory cytokines, and restoring intestinal barriers. This work demonstrated the synergistic therapy of intestinal diseases based on alginate-encapsulated probiotics and a clinical drug, which provided an extensive method to improve the therapeutic effect of oral microecologics.