pH/ROS Dual-Sensitive Natural Polysaccharide Nanoparticles Enhance “One Stone Four Birds” Effect of Rhein on Ulcerative Colitis

Abstract

Rhein (RH), a natural anthraquinone compound, is considered an effective treatment candidate for ulcerative colitis (UC), whose multiple biological activities contribute to UC, including anti-inflammation, antioxidation, intestinal barrier repair, and microflora regulation. However, the application of RH is severely limited by its low water solubility, low bioavailability, and poor colonic targeting. Although some nanoparticles have been developed for the oral delivery of RH, most of them mainly highlighted only one effect of some drug delivery strategies but the above multiple biological activities. Therefore, a multiple polysaccharide-based nanodelivery system, comprising chitosan (CS) and fucoidan (FU), with pH/reactive oxygen species (ROS) sensitivity and mucosal adhesion, was developed and first used to load RH as a comprehensive treatment for UC. Briefly, RH-F/C-NPs were prepared using the polyelectrolyte self-assembly method; the average size of RH-F/C-NPs was 233.1 ± 5.7 nm, and the encapsulation rate of RH was 93.67 ± 1.60%. And it could maintain gastric stability and release RH in the colon with the designed pH/ROS sensitivity contributed by the polysaccharide-based structures. Cellular uptake experiments showed that both NCM 460 cells and RAW 264.7 cells had a good uptake of RH-F/C-NPs. Importantly, the effects of RH were highlighted in in vivo experiments, the results of which showed that RH-F/C-NPs could significantly reduce DSS-induced inflammation by inhibiting the TLR4/NF-κB-mediated anti-inflammatory pathway, the Nrf2/HO-1-mediated antioxidant pathway, colonic mucosal barrier repair, and intestinal microflora regulation. In addition, pharmacokinetic studies have shown that F/C-NPs contribute to the increase in the plasma concentration and the accumulation of RH in the colon to some extent. In short, this study is the first to develop an oral multiple polysaccharide-based nanosystem with pH/ROS dual sensitivity to study the "one stone four birds" therapeutic effect of RH on UC.

Thermosensitive hydrogel with emodin-loaded triple-targeted nanoparticles for a rectal drug delivery system in the treatment of chronic non-bacterial prostatitis

“…Prostate, rectal, and other organs (heart, liver, spleen, lung, and kidney) tissues were collected under light-proof conditions and embedded in Optimal Cutting Temperature compounds, sectioned, and stained with DAPI to detect C 6 accumulation using CLSM. Furthermore, in order to evaluate the retention time of the thermosensitive gel in the rat rectum, we collected the residual gel in the rectum at different time points (1, 3, 6, 12, 24 h) after rectal administration of the HA/LF@EMO-NPs Gel, and the content of EMO in the gel was detected by HPLC (EMO Content = EMO (ug)/Gel (g)) [ 40 , 41 ].…”

Bioinspired and biomimetic strategies for inflammatory bowel disease therapy

“…5 Of note, chitosan is sensitive to physiologically acidic environments, which can result in the untimely release of loaded drugs and affect its effectiveness as a carrier. As a common drug carrier, chitosan is often combined with negatively charged polysaccharides through electrostatic interactions, including alginate, 148,156 hyaluronic acid, 157 pectin 158 and fucoidan, 159 to enhance its drug-delivery capability. A smart cauliflower-like carrier for astaxanthin delivery to relieve colon inflammation was reported by Zhang et al The smart cauliflower-like carrier consisted of caseinate, chitosan-triphenylphosphine (TPP) and sodium alginate combined through electrostatic interactions 148 (Fig.…”

Marine biomaterials in biomedical nano/micro-systems

“…Created with BioRender.com Nanoparticles for oral small molecule drug delivery Recently, chitosan or chitosan derivatives have been extensively used to be prepared as core–shell nanomaterials, and microcapsules for improving the payload stability, enhanced payload solubility, controlled drug release, and increased cellular uptake efficiency of a variety of hydrophobic agents or components (e.g., silymarin, curcumin, antibiotics, chemotherapy drugs camptothecin, etc. ), thereby enhancing their oral bioavailability [ 16 , 30 – 32 ]. Those design mainly focus on promoting the particle accumulation continuously in the mucosa due to chitosan adhesion effects and hence enhancing the bioavailability of drug for gastrointestinal diseases.…”

“…This also offers potential synergistic therapeutic effects while facilitating the active targeting of fucoidan-based nanomaterials [ 160 , 161 ]. Fucoidan-based and fucoidan-coated nanomaterials were designed based on the specificity of fucoidan ligands to P-selectin receptors in order to target endogenous and stimulus-induced overexpressed P-selectin [ 162 – 165 ].…”