Encapsulation of Escherichia coli strain Nissle 1917 in a chitosan―alginate matrix by combining layer-by-layer assembly with CaCl2 cross-linking for an effective treatment of inflammatory bowel diseases

Abstract

Escherichia coli strain Nissle 1917 (EcN) has been widely shown to effectively treat inflammatory bowel diseases (IBDs). Unfortunately, after oral administration, EcN viability dramatically decreases due to severe environmental factors, including low gastric pH, temperature and osmotic pressure. To address these challenges and improve oral bio-availability, this study utilized layer-by-layer assembly (LbL) and ionic cross-linking with CaCl2 as a method of EcN encapsulation (GEcN). Upon examination, GEcN cells were shown to maintain their ability to grow and proliferate, but had a slightly longer stationary phase (10 h) relative to free EcN (4 h). When exposed to simulated gastric fluid (SGF), a higher number of GEcN cells survived up to 12 h when compared to the other groups. To assess the therapeutic effect of EcN encapsulation in vivo, a TNBS-induced colitis rat model was established. When compared with the oral administration of free EcN, GEcN exhibited a significantly enhanced anti-inflammatory effect. Furthermore, GEcN treatment showed a lower disease activity index (DAI), decreased pro-inflammatory cytokine expression (MPO, TNF-α, IL-6) and increased anti-inflammatory cytokine expression (IL-10). Additionally, rats that received GEcN had much higher ZO-1 expression levels. These results suggest that EcN encapsulation in a chitosan―alginate matrix when utilizing the LbL assembly with CaCl2 cross-linking can improve probiotic viability in a gastric environmental and thereby offer a more effective treatment for IBDs.