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Metformin Hydrochloride Mucosal Nanoparticles-Based Enteric Capsule for Prolonged Intestinal Residence Time, Improved Bioavailability, and Hypoglycemic Effect

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  • Advancements in Modified-release Oral Drug Delivery - Delivery throughout the Gastro-intestinal Tract
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Abstract

Metformin hydrochloride enteric-coated capsule (MH-EC) is a commonly used clinical drug for the treatment of type 2 diabetes. In this study, we described a metformin hydrochloride mucosal nanoparticles enteric-coated capsule (MH-MNPs-EC) based on metformin hydrochloride chitosan mucosal nanoparticles (MH-CS MNPs) and its preparation method to improve the bioavailability and hypoglycemic effect duration of MH-EC. In intestinal adhesion study, the residue rates of free drugs and mucosal nanoparticles were 10.52% and 67.27%, respectively after cleaned with PBS buffer. MH-CS MNPs could significantly improve the efficacy of MH and promote the rehabilitation of diabetes rats. In vitro release test of MH-MNPs-EC showed continuous release over 12 h, while commercial MH-EC released completely within about 1 h in intestinal environment (pH 6.8). Pharmacokinetic study was performed in beagle dogs compared to the commercial MH-EC. The durations of blood MH concentration above 2 μg/mL were 9 h for MH-MNPs-EC versus 2 h for commercial MH-EC. The relative bioavailability of MH-MNPs-EC was determined as 185.28%, compared with commercial MH-EC. In conclusion, MH-CS MNPs have good intestinal adhesion and can significantly prolong the residence time of MH in the intestine. MH-MNPs-EC has better treatment effect compared with MH-EC, and it is expected to be a potential drug product for the treatment of diabetes because of its desired characteristics.

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Acknowledgements

We thank Dr. Jiayi Chen from Ascendia Pharmaceuticals, Inc., for his support in writing of the thesis.

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); Key Project of Key Laboratory of Xin’an Medicine (Anhui University of Chinese Medicine); and Ministry of Education (No. 2020xayx02).

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  1. Wenjie Lu, Lingfei Yu and Lujun Wang contributed equally.

Authors and Affiliations

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

    Wenjie Lu & Haiping Hao

  2. 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

    Lingfei Yu, Lujun Wang, Manman Li, Zijun Wu, Shengqi Chen & Rongfeng Hu

  3. Anhui Huangshan Capsule Co. Ltd., Huangshan, 242700, Anhui, China

    Songlin Liu

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  1. Wenjie Lu
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Contributions

Participated in research design: Wenjie Lu, Lingfei Yu, Lujun Wang, Rongfeng Hu

Conducted experiments: Wenjie Lu, Lingfei Yu, Lujun Wang, Manman Li, Zijun Wu

Contributed new reagents or analytic tools: Wenjie Lu, Shengqi Chen, Rongfeng Hu, Haiping Hao

Performed data analysis: Wenjie Lu, Lujun Wang, Shengqi Chen, Rongfeng Hu, Haiping Hao

Wrote or contributed to the writing of the manuscript: Wenjie Lu, Lujun Wang, Lingfei Yu, Manman Li, Zijun Wu, Shengqi Chen, Rongfeng Hu, Haiping Hao

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Correspondence to Shengqi Chen, Rongfeng Hu or Haiping Hao.

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Lu, W., Yu, L., Wang, L. et al. Metformin Hydrochloride Mucosal Nanoparticles-Based Enteric Capsule for Prolonged Intestinal Residence Time, Improved Bioavailability, and Hypoglycemic Effect. AAPS PharmSciTech 24, 31 (2023). https://doi.org/10.1208/s12249-022-02402-w

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