Oral delivery of chitosan-coated PLGA nanoemulsion loaded with artesunate alleviates ulcerative colitis in mice

Artesunate (ARS) has been shown to have a protective effect on ulcerative colitis (UC) in mice. However, its lack of targeting and short half-life severely hamper its efficacy. In this study, polylactic acid-glycolic acid copolymer (PLGA) and chitosan (CS) double emulsification solvent volatilisation method was used to prepare a stable nanoemulsion loaded with ARS (CPA). The in vitro drug release profile was detected using dialysis and the potential protective effect was evaluated in an experimental ulcerative colitis (UC) model induced by oral administration of dextran sulphate sodium (DSS). The results suggested that the mean droplet diameter of CPA nanoemulsion is 409.9 ± 9.21 nm, the polydispersity index is 0.17 ± 0.01 and the zeta potential is 40.07 ± 1.65 mV. The cumulative release curve showed the ARS was mainly released at pH 7.4, which is similar to the colonic environment. Oral administration of CPA effectively relieved DSS-induced clinical symptoms by lowering the body weight loss, disease activity index (DAI) score and impressively maintained tight junction protein expression in colon tissue when compared to the blank nanoemulsion control. Meanwhile, CPA remarkably suppressed TLR4/NF-κB pathway activation and mRNA levels of proinflammatory cytokines (IL-1β, IL-6, and TNF-α) while enhanced levels of IL-10 and CD206. In addition, the effect of CPA was slightly better than that of injecting ARS. Therefore, this study demonstrates a convenient drug delivery system for oral administration of ARS that potentially helps to target colonic tissue and alleviate UC. [Display omitted] •PLGA was selected as sustained-release polymer and chitosan as colon responsive polymers.•CPA can efficiently retain the ARS until reaching the colon.•CPA improved intestinal barrier dysfunction via maintain the expressions of TJs proteins.•CPA suppressed DSS induced the expression and activation of key proteins of the TLR-4/NF-κB pathway.