An efficient enzyme-triggered controlled release system for colon-targeted oral delivery to combat dextran sodium sulfate (DSS)-induced colitis in mice

Abstract

Oral route colon-targeted drug delivery systems (CDDSs) are desirable for the treatment of ulcerative colitis (UC). However, CDDSs are challenging owing to the physiological and anatomical barriers associated with the gastrointestinal tract (GIT). In this study, we developed an effective enzyme-triggered controlled release system using curcumin–cyclodextrin (CD–Cur) inclusion complex as core and low molecular weight chitosan and unsaturated alginate resulting nanoparticles (CANPs) as shell. The formed CD–Cur–CANPs showed a narrow particle-size distribution and a compact structure. In vitro drug release determination indicated that CD–Cur–CANPs showed pH-sensitive and α-amylase-responsive release characteristics. Furthermore, in vivo experiments demonstrated that oral administration of CD–Cur–CANPs had an efficient therapeutic efficacy, strong colonic biodistribution and accumulation, rapid macrophage uptake, promoted colonic epithelial barrier integrity and modulated production of inflammatory cytokines, reshaped the gut microbiota in mice with dextran sodium sulfate (DSS)-induced colitis. Taken together, our synthetic CD–Cur–CANPs are a promising synergistic colon-targeted approach for UC treatment.

Changes of Intestinal Flora and Its Relationship with Nutritional Status for Patients with Cancer Pain

“…In the digestive tract, the patient's mucosa was correspondingly damaged, and the ability to absorb nutrients was significantly reduced [ 20 ]. The body's vitamin D level was significantly deficient, and the risk of diffuse muscle pain in the waist, pelvis, and lower limbs was significantly increased [ 21 ]. It had been confirmed in foreign studies [ 22 – 24 ] that the level of 25 hydroxyvitamin D showed a significant correlation with the dosage of opioids in tumor patients.…”

The role of functional oligosaccharides as prebiotics in ulcerative colitis

“…The integrity of the gut epithelial barrier is compromised in UC patients, including decreased expression of tight junction proteins (ZO-1, occludin and claudin-1), increased intestinal mucosal permeability and impaired intestinal mucosal tissue. [21][22][23][24] Meanwhile, the composition of the gut microbiota in UC patients changes significantly, resulting in more flagellin and lipopolysaccharide (LPS) in the gut microbiota, promoting the expression of pro-inflammatory factors and causing intestinal inflammation. In addition, bacteria are more likely to invade the dense mucus layer, making it easier for harmful bacteria to contact intestinal mucosal cells, so as to stimulate the production of proinflammatory cytokines and then recruit immune cells.…”

Application of chitosan/alginate nanoparticle in oral drug delivery systems: prospects and challenges

“…In our previous study, an effective enzyme-triggered controlled release system using a curcumin-cyclodextrin (CD-Cur) inclusion as the core and CANPs as the shell (Li et al., 2021 ). This specific colon-targeted drug delivery system showed significant pH-dependent properties, protecting the drugs through GIT.…”