Lentinan-Based Oral Nanoparticle Loaded Budesonide With Macrophage-Targeting Ability for Treatment of Ulcerative Colitis

Abstract

Ulcerative colitis (UC) is a global, chronic, and refractory disease. Corticosteroids are first-line drugs for the treatment of UC but also cause adverse side effects. Budesonide (BUD), a corticosteroid with relatively low side effects, has been approved by the Food and Drug Administration for use as enteric capsules (Entocort EC) for the treatment of inflammatory bowel disease (IBD). However, this formulation lacks specific targeting ability to UC lesions. Herein, we describe the development of an advanced macrophage-targeted oral lentinan (LNT)–based nanoparticles (NPs) loaded BUD for treatment of UC. Briefly, LNT was used as a food source and natural carrier to load BUD by a simple solvent evaporation method to form LNT/BUD-NPs. LNT showed good loading capacity with high encapsulation and loading efficiencies to BUD of approximately 92.19 and 9.58%, respectively. Evaluation of the gastric stability of LNT/BUD-NPs indicated that LNT could effectively protect BUD from gastric acid and digestive enzymes. The release behavior and transmission electron microscopy image of LNT/BUD-NPs in the intestinal content of mice confirmed that intestinal flora can promote BUD release from LNT. Moreover, evaluation of cellular uptake showed that LNT/BUD-NPs could specifically target macrophages and enhance their uptake rate via the Dectin-1 receptor. In biodistribution studies, LNT/BUD-NPs were able to efficiently accumulate in the inflamed colon of mice. As expected, LNT/BUD-NPs could significantly alleviate inflammation by inhibiting the TLR4/MyD88/NF-κB signaling pathway. Therefore, LNT/BUD-NPs have the advantages of good gastric stability, release mediated by mouse intestinal content, macrophage-targeting, and anti-UC effects. These advantages indicate LNT-based NPs are a promising oral drug delivery system for UC therapy.

Lentinan improves intestinal inflammation and gut dysbiosis in antibiotics-induced mice

“…Lentinan had a potential anti-inflammatory effect on LPS-induced intestinal inflammatory response of juvenile taimen (Hucho taimen, Pallas) 20 . Emerging data have demonstrated that lentinan-based oral nanoparticle-loaded Budesonide (NT/BUD-NPs) significantly alleviated Ulcerative Colitis by targeting ability for treatment 21 . Moreover, lentinan significantly improved gut microbiota dysbiosis by decreasing phylum Proteobacteria and Epsilonbacteraeota 22 .…”

Protective mechanisms of Zanthoxylum bungeanum essential oil on DSS-induced ulcerative colitis in mice based on a colonic mucosal transcriptomic approach

“…Ulcerative colitis (UC) is also called chronic nonspecific ulcerative colitis. 1 It is one of the two main forms of inflammatory bowel disease (IBD) 2 that typically occurs in the rectum and proceeds proximately, even involving the mucosa in a symmetric uninterrupted pattern. 3 UC patients commonly exhibit weight loss, abdominal pain, and bloody diarrhoea, which severely reduce the quality of life of the individual and even lead to death.…”

Polymer-Based Nanosystems—A Versatile Delivery Approach

“…Other natural polymers that have attracted research interest for delivery purposes include, but are not limited to, glycogen [114][115][116], starch [114,[117][118][119][120], lignin [121,122], heparin [123,124], lentinan [14,125,126], and chondroitin sulfate [127][128][129].…”