Oral Core–Shell Nanoparticles Embedded in Hydrogel Microspheres for the Efficient Site-Specific Delivery of Magnolol and Enhanced Antiulcerative Colitis Therapy

Abstract

Although magnolol (Mag), an anti-inflammatory natural compound, has been demonstrated to play protective effects on ulcerative colitis (UC), its application as an alternative therapeutic reagent for UC treatment is still greatly impeded due to its poor stability in the gastrointestinal tract and insufficient accumulation in the inflamed colon lesion. Nano-/microsized drug delivery systems can potentially overcome some challenges regarding the oral administration of phytochemicals, which still confront premature early drug release, degradation of NPs, or the sustained drug release of MPs. In this study, we primarily loaded Mag into the core–shell zein-based nanoparticles with chondroitin sulfate coating (Mag@CS-Zein NPs) with an average size of 142.27 ± 5.11 nm, showing significant macrophage-targeting and enhanced colon epithelial cellular uptake capacity. Then, we embedded Mag@CS-Zein NPs into hydrogel microspheres via an electrospraying technology. The Mag@CS-Zein NPsinMPs presented a uniform-sized sphere with an average size of 164.36 ± 6.29 μm and sustained drug-release profiles. Compared to CS-Zein NPs, the developed CS-Zein NPsinMPs exhibited prolonged colon retention on the inflammatory surface, as seen from ex vivo and in vivo imaging fluorescence adhesion experiments. Based on the advantage of the combination of hybrid nanoparticles-in-microparticles, oral administration of Mag@CS-Zein NPsinMPs significantly alleviated colitis symptoms in DSS-treated mice by regulating the expression levels of proinflammatory cytokines (TNF-α, IL-6, and IL-1β) and anti-inflammatory cytokines (IL-10) and factor accelerated colonic mucosal barrier repair via upregulating the expression of ZO-1 and occludin. This study provides great insights into the oral drug delivery of natural compounds for UC therapy.

Protective Effects of Amauroderma rugosum on Doxorubicin-Induced Cardiotoxicity through Suppressing Oxidative Stress, Mitochondrial Dysfunction, Apoptosis, and Activating Akt/mTOR and Nrf2/HO-1 Signaling Pathways

“…Oxidative stress is considered to be one of the main causes of Dox-induced cardiac injury [ 23 ] as an imbalance between ROS and antioxidants can lead to oxidative stress [ 24 , 25 ]. Sustained oxidative stress caused by Dox can reduce the mitochondrial membrane potential, which induces mitochondrial dysfunction and cell apoptosis and ultimately leads to cardiomyocyte damage [ 26 ].…”

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

“…After 24 h of treatment, the cell culture medium was collected, in which IL-10, IL-1β, TNF-α, and IL-6 were detected using ELISA kits (Multi Science (Lianke) Biotech, Co., Ltd). 29…”

Colon-specific delivery of isoliquiritigenin by oral edible zein/caseate nanocomplex for ulcerative colitis treatment

“…The severity of colitis was histologically evaluated by H&E staining and PAS staining of colon tissue. H&E staining and PAS staining reflected the inflammatory damage of colon tissue and the situation of colonic mucus goblet cells, respectively (Wang et al, 2021). The representative picture was shown in Figure 6A, the colonic tissue of the control mice showed no signs of inflammation or destruction of healthy tissue morphology.…”

“…The main symptoms of ulcerative colitis were diarrhea, hematochezia, and weight loss (Wang et al, 2021). Therefore, DAI score, weight, and colonic length changes were used as evaluation indexes of disease severity in mice.…”