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Effect of Size and Loading of Retinoic Acid in Polyvinyl Butyrate Nanoparticles on Amelioration of Colitis.

ABSTRACT: Butyrate has been used in the treatment of inflammatory bowel diseases (IBD). However, the controlled release of butyrate has been indicated to be necessary in order to avoid the side effects verified at high concentrations. We previously developed nanoparticles (NPs) of polyvinyl butyrate (PVBu) as an oral butyrate donor for the controlled release of butyrate for the treatment of colitis. To examine the effect of the size of NPs on the therapeutic effect of colitis, here we prepared PVBu NPs with different sizes (100 nm and 200 nm). Both sizes of PVBu NPs significantly suppressed the inflammatory response in macrophages in vitro. PVBu NPs with 200 nm showed better effects on the amelioration of colitis compared with the 100 nm-NPs. We found unexpectedly that 200 nm-NP incorporated with all-trans retinoic acid (ATRA) showed a much better therapeutic effect than those with unloaded 200 nm-NPs, although ATRA alone was reported to worsen the inflammation. The synergistic effect of ATRA with butyrate shows evidence of being a promising approach for IBD treatment.

SUBMITTER: Li J

PROVIDER: S-EPMC8124360 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

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Effect of Size and Loading of Retinoic Acid in Polyvinyl Butyrate Nanoparticles on Amelioration of Colitis.

Li Jinting J Mu Yunmei Y Liu Yiwei Y Kishimura Akihiro A Mori Takeshi T Katayama Yoshiki Y

Polymers 20210502 9

Butyrate has been used in the treatment of inflammatory bowel diseases (IBD). However, the controlled release of butyrate has been indicated to be necessary in order to avoid the side effects verified at high concentrations. We previously developed nanoparticles (NPs) of polyvinyl butyrate (PVBu) as an oral butyrate donor for the controlled release of butyrate for the treatment of colitis. To examine the effect of the size of NPs on the therapeutic effect of colitis, here we prepared PVBu NPs wi ...[more]

PMID: 34063206

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Project description:BackgroundDamage to the healthy intestinal epithelial layer and regulation of the intestinal immune system, closely interrelated, are considered pivotal parts of the curative treatment for inflammatory bowel disease (IBD). Plant-based diets and phytochemicals can support the immune microenvironment in the intestinal epithelial barrier for a balanced immune system by improving the intestinal microecological balance and may have therapeutic potential in colitis. However, there have been only a few reports on the therapeutic potential of plant-derived exosome-like nanoparticles (PENs) and the underlying mechanism in colitis. This study aimed to assess the therapeutic effect of PENs from Panax ginseng, ginseng-derived exosome-like nanoparticles (GENs), in a mouse model of IBD, with a focus on the intestinal immune microenvironment.MethodTo evaluate the anti-inflammatory effect of GENs on acute colitis, we treated GENs in Caco2 and lipopolysaccharide (LPS) -induced RAW 264.7 macrophages and analyzed the gene expression of pro-inflammatory cytokines and anti-inflammatory cytokines such as TNF-α, IL-6, and IL-10 by real-time PCR (RT-PCR). Furthermore, we further examined bacterial DNA from feces and determined the alteration of gut microbiota composition in DSS-induced colitis mice after administration of GENs through 16S rRNA gene sequencing analysis.ResultGENs with low toxicity showed a long-lasting intestinal retention effect for 48 h, which could lead to effective suppression of pro-inflammatory cytokines such as TNF-α and IL-6 production through inhibition of NF-κB in DSS-induced colitis. As a result, it showed longer colon length and suppressed thickening of the colon wall in the mice treated with GENs. Due to the amelioration of the progression of DSS-induced colitis with GENs treatment, the prolonged survival rate was observed for 17 days compared to 9 days in the PBS-treated group. In the gut microbiota analysis, the ratio of Firmicutes/Bacteroidota was decreased, which means GENs have therapeutic effectiveness against IBD. Ingesting GENs would be expected to slow colitis progression, strengthen the gut microbiota, and maintain gut homeostasis by preventing bacterial dysbiosis.ConclusionGENs have a therapeutic effect on colitis through modulation of the intestinal microbiota and immune microenvironment. GENs not only ameliorate the inflammation in the damaged intestine by downregulating pro-inflammatory cytokines but also help balance the microbiota on the intestinal barrier and thereby improve the digestive system.

Dataset Information

Effect of Size and Loading of Retinoic Acid in Polyvinyl Butyrate Nanoparticles on Amelioration of Colitis.

Publications

Effect of Size and Loading of Retinoic Acid in Polyvinyl Butyrate Nanoparticles on Amelioration of Colitis.

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