Berberine-Loaded Carboxylmethyl Chitosan Nanoparticles Ameliorate DSS-Induced Colitis and Remodel Gut Microbiota in Mice.

Luqing Zhao,Danyan Li,Shengsheng Zhang,Xueying Du,Yuxin Li,Chao Li,Jiaxin Tian,Xiuhong Kang,Wenlin Dai

doi:10.3389/fphar.2021.644387

Abstract

Inflammatory bowel disease (IBD) is a refractory disorder characterized by chronic and recurrent inflammation. The progression and pathogenesis of IBD is closely related to oxidative stress and irregularly high concentrations of reactive oxygen species (ROS). A new oxidation-responsive nano prodrug was constructed from a phenylboronic esters-modified carboxylmethyl chitosan (OC-B) conjugated with berberine (BBR) that degrades selectively in response to ROS. The optimized micelles exhibited well-controlled physiochemical properties and stability in a physiological environment. OC-B-BBR micelles could effectively encapsulate the anti-inflammatory drug berberine and exhibit ideal H2O2-triggered release behavior as confirmed by in vitro drug loading and release studies. The in vivo anti-inflammatory effect and regulation of gut microbiota caused by it were explored in mice with colitis induced by dextran sodium sulfate (DSS). The results showed that OC-B-BBR significantly ameliorated colitis symptoms and colon damage by regulating the expression levels of IL-6 and remodeling gut microbiota. In summary, this study exhibited a novel BBR-loaded Carboxylmethyl Chitosan nano delivery system which may represent a promising approach for improving IBD treatment.

Highlights

Inflammatory bowel disease (IBD) is a refractory gastrointestinal disorder characterized by chronic and recurrent inflammation
Carboxylmethyl chitosan was chosen as a carrier to improve solubility and biocompatibility of micelles for drug delivery
The synthesis route of the nanocarrier OC-B-BBR was depicted in Supplementary Scheme S1

Summary

Introduction

Inflammatory bowel disease (IBD) is a refractory gastrointestinal disorder characterized by chronic and recurrent inflammation. IBD has a high incidence in the United States (more than 1 million) and in Western Europe (2.5 million), and has evolved into a widespread disease with increasing prevalence all over the world (Kaplan, 2015). The pathogenesis of IBD is still not fully understood, but it is mainly considered to be associated with environmental factors, host genetic susceptibility, changes in intestinal flora and intestinal epithelial barrier dysfunction, and other factors (Zundler and Neurath, 2015). Oxidative stress plays an essential role in the pathogenesis and progression of IBD (Tian et al, 2017), and leads to excessive ROS accumulation. Biopsies from patients with IBD demonstrate abnormally high levels of ROS at the site of the lesion, with mucosal ROS concentrations increasing from 10- to 100-fold (Simmonds et al, 1992; Lih-Brody et al, 1996)

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Results

Conclusion