An oral delivery vehicle based on konjac glucomannan acetate targeting the colon for inflammatory bowel disease therapy

Abstract

Orally administered colon-targeted delivery vehicles are of major importance in the treatment of inflammatory bowel disease (IBD). However, it remains a challenge to maintain the integrity of such delivery vehicles during treatment, particularly in the gastric environment, which may cause untimely drug release before reaching the targeted colon. Herein, an oral colon-targeted drug delivery system (OCDDS) based on acetylated konjac glucomannan (AceKGM) has been developed in this work, which accomplishes colonic localization release and targets local inflammatory macrophages. The AceKGM nanoparticle-loading curcumin (Cur) was successfully fabricated by emulsion solvent evaporation techniques. DLS, AFM, and SEM were used in order to evaluate the nanoparticles’ diameter as well as their in vitro drug release profile, and reactive oxygen species (ROS) scavenging results showed that the OCDDS considerably retained the activity of Cur treated with simulated gastric fluid (SGF) and controllably released in simulated intestinal fluid (SIF). In addition, the adhesion experiment results indicated that the nanoparticle could accumulate on the colonic macrophages. Evaluations in colitis mice showed that the treatment significantly alleviated the symptoms of colitis by decreasing the local level of myeloperoxidase (MPO) and the disease activity index (DAI) score in mice. In summary, the results of our research demonstrate that Cur–AceKGM nanoparticles exhibit significantly improved therapeutic efficacy compared to orally administered free Cur and can be developed as an effective drug delivery vehicle for IBD treatment.

Nanoparticle-Based Drug Delivery Systems for Inflammatory Bowel Disease Treatment

“…Wang et al developed a naturally occurring polysaccharide-based NP that targets binding to macrophage mannose receptors. 75 According to the experimental results, NPs exhibited 81% drug release within 48 h, and the MPO levels of the mice were decreased. The NPs offer sustained release of curcumin and effective therapeutic outcomes compared to oral free curcumin administration ( Figure 6 ).…”

“…It also increases the degree of endocytosis and the bioadhesion of drug agents to particular cells ( Figure 1F ). 75–94 …”

Medicinal plant-based drug delivery system for inflammatory bowel disease

“…This study used an ex vivo murine colonic explant from an inflammation model and found that NPL/Cur is not only on the surface of epithelial cells, but also can penetrate into the intestinal wall, with stronger targeting (Salah et al, 2022). Curcumin encapsulated by solid binary lipid nanoparticles (C-SBLNs) also has good gastrointestinal stability, and prolonged drug release up to 24 h. Oral administration of C-SBLNs can reduce leukocyte infiltration, oxidative stress and proinflammatory cytokines (TNF-α), restore colon structure in DSS-induced colitis mice (Sharma et al, 2019) (Wang et al, 2022). Drug delivery systems based on pH and/or enzyme also have good application prospects in IBD.…”

“…At 48 h, the release of Cur-AceKGM NPs in SIF can reach 81%. Cur-AceKGM NPs can decrease the colon local level of MPO and DAI score, significantly alleviate the symptoms of colitis ( Wang et al, 2022 ). Drug delivery systems based on pH and/or enzyme also have good application prospects in IBD.…”