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Mucus-Penetrating Alginate-Chitosan Nanoparticles Loaded with Berberine Hydrochloride for Oral Delivery to the Inflammation Site of Ulcerative Colitis

  • Research Article
  • Theme: Advancements in Modified-release Oral Drug Delivery - Delivery throughout the Gastro-intestinal Tract
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A Correction to this article was published on 09 August 2022

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Abstract

The rectal enemas of berberine hydrochloride (BH) have emerged as one of the most effective strategies in the clinical treatment of ulcerative colitis (UC). However, oral dosages of BH exhibit a poor anti-inflammatory effect of UC, which may attribute to premature absorption of BH by the upper gastrointestinal tract. Moreover, the thick colonic mucus layer obstructs the penetration of the drug, resulting in low bioavailability to the inflammatory site of the colon. The aim of this study was to develop the mucus-penetrating sodium alginate-chitosan nanoparticles (SA-CS NPs) for oral delivery of BH to the site of colonic ulcer lesions. BH-loaded SA-CS NPs were developed through the ionic gelation method and analyzed for physicochemical characteristics, release performance, penetrability, site retention, and therapeutic efficacy. The results showed that the NPs have a particle size of 257 nm with a negative charge, presenting desired pH-dependent release behavior. The permeation studies elucidated that negatively charged SA-CS NPs had 2.9 times higher mucus penetration ability than positively charged CS NPs. An ex vivo retention study indicated the high retention of BH-SA-CS NPs at the colon site for more than 16 h. In vivo therapeutic effectiveness demonstrated that the prepared NPs could not only alleviate colonic injury by decreasing the disease activity index and colon mucosa damage index, but also improve the immunologic function by decreasing the spleen index. In conclusion, the BH-SA-CS NPs could enhance the mucus permeability and deliver drugs to the colonic inflammation site, providing new insights into improving the therapeutic effect of UC.

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Acknowledgements

We thank the Anhui Province Key Laboratory of Pharmaceutical Technology and Application for providing an experimental platform. We thank Prof. BangXing Han from the West Anhui University for valuable scientific advice.

Funding

This project was funded by the National Natural Science Foundation of China (No. 81973488, No. 22003002); Key Project of Natural Science Foundation for the Higher Education Institutions of Anhui Province (GXXT-2020-025(10-4); KJ2019A0451; KJ2020A0382); Anhui Province Key Laboratory of Pharmaceutical Preparation Technology and Application (2021KFKT04; 2021KFKT07; 2021hxts03); Key Laboratory of Xin’an Medicine (Anhui University of Chinese Medicine), Ministry of Education (No. 2020xayx02); and Natural Science Foundation of Anhui Province (2108085QH371).

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  1. Lingfeng Sun, Xiangjiang Nie, and Wenjie Lu contributed equally to this work.

Authors and Affiliations

  1. Anhui Province Key Laboratory of Pharmaceutical Technology and Application, Key Laboratory of Xin’an Medicine Ministry of Education, Anhui Province Key Laboratory of Chinese Medicinal Formula, Anhui University of Chinese Medicine, Hefei, 230038, Anhui, China

    Lingfeng Sun, Xiangjiang Nie, Wenyou Fang, Song Gao, Shengqi Chen & Rongfeng Hu

  2. School of Pharmacy, China Pharmaceutical University, Nanjing, 210009, Jiangsu, China

    Wenjie Lu

  3. Department of Pharmacy, School of Pharmacy, Nanjing Medical University, Nanjing, 210009, Jiangsu, China

    Qing Zhang

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Contributions

Participated in research design: Lingfeng Sun, Xiangjiang Nie, Song Gao, Wenjie Lu

Conducted experiments: Lingfeng Sun, Xiangjiang Nie, Song Gao, Wenjie Lu

Contributed new reagents or analytic tools: Qing Zhang, Wenyou Fang, Shengqi Chen, Rongfeng Hu

Performed data analysis: Lingfeng Sun, Xiangjiang Nie, Song Gao, Wenyou Fang

Wrote or contributed to the writing of the manuscript: Lingfeng Sun, Xiangjiang Nie, Song Gao, Wenjie Lu, Wenyou Fang, Shengqi Chen, Rongfeng Hu

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Correspondence to Song Gao, Shengqi Chen or Rongfeng Hu.

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Sun, L., Nie, X., Lu, W. et al. Mucus-Penetrating Alginate-Chitosan Nanoparticles Loaded with Berberine Hydrochloride for Oral Delivery to the Inflammation Site of Ulcerative Colitis. AAPS PharmSciTech 23, 179 (2022). https://doi.org/10.1208/s12249-022-02327-4

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