Charge-reversible and biodegradable chitosan-based microgels for lysozyme-triggered release of vancomycin

Journal of Advanced Research, vol. 43, pp. 87–96

Abstract

INTRODUCTION: High-dose drug administration for the conventional treatment of inflammatory bowel disease induces cumulative toxicity and serious side effects. Currently, few reports have introduced smart carriers for intestinal inflammation targeting toward the treatment of inflammatory bowel disease. OBJECTIVES: For the unique lysozyme secretory microenvironment of the inflamed intestine, vancomycin-loaded chitosan-polyaniline microgels (CH-PANI MGs) were constructed for lysozyme-triggered VM release. METHODS: Aniline was first grafted to chitosan to form polymers that were crosslinked by glutaraldehyde to achieve CH-PANI MGs using the inverse (water-in-oil) miniemulsion method. Interestingly, CH-PANI MGs exhibit polyampholyte behaviour and display charge-reversible behaviour (positive to negative charges) after treatment with a NaCl solution. RESULTS: The formed negatively charged N-CH-PANI MG aqueous solution is employed to load cationic vancomycin with a satisfactory loading efficiency of 91.3%, which is significantly higher than that of chitosan-based MGs. Moreover, N-CH-PANI MGs present lysozyme-triggered biodegradation and controllable vancomycin release upon the cleavage of glycosidic linkages of chitosan. In the simulated inflammatory intestinal microenvironment, vancomycin is rapidly released, and the cumulative release reaches approximately 76.9%. Remarkably, N-CH-PANI@VM MGs not only exhibit high resistance to harsh gastric acidity but also prevent the premature leakage of vancomycin in the healthy gastrointestinal tract. Encouragingly, the N-CH-PANI@VM MGs show obvious antibacterial activity against Staphylococcus aureus at a relatively low concentration of 20 μg/mL. CONCLUSION: Compared to other pH-responsive carriers used to treat inflammatory bowel disease, the key advantage of lysozyme-responsive MGs is that they further specifically identify healthy and inflammatory intestines, achieving efficient inflammatory bowel disease treatment with few side effects. With this excellent performance, the developed smart MGs might be employed as a potential oral delivery system for inflammatory bowel disease treatment.

Authors 6

1. Xin Li Aachen DWI-Leibniz-Institute for Interactive Materials e.V Institute of Technical and Macromolecular Chemistry Institute of Technical and Macromolecular Chemistry

   DWI – Leibniz Institute for Interactive Materials · Zhejiang University of Technology · RWTH Aachen University

   Affiliation as printed

   Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, China; DWI-Leibniz-Institute for Interactive Materials e.V, 52056 Aachen, Germany; Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, 52074 Aachen, Germany

   Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, China

   DWI-Leibniz-Institute for Interactive Materials e.V, 52056 Aachen, Germany

   Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, 52074 Aachen, Germany

2. Laura Hetjens

   Zhejiang University of Technology

   Affiliation as printed

   Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, China

3. Nadja Wolter Aachen DWI-Leibniz-Institute for Interactive Materials e.V

   DWI – Leibniz Institute for Interactive Materials

   Affiliation as printed

   DWI-Leibniz-Institute for Interactive Materials e.V, 52056 Aachen, Germany

4. Helin Li corresponding

   Zhejiang University of Technology

   Affiliation as printed

   Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, China. Electronic address: lihelin109280@zjut.edu.cn

   Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, Zhejiang University of Technology, Hangzhou 310014, China

5. Xiangyang Shi corresponding

   Donghua University · Centro de Química da Madeira · Universidade da Madeira

   Affiliation as printed

   College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China; CQM-Centro de Química da Madeira, Universidade da Madeira, Campus da Penteada, 9000-390 Funchal, Portugal. Electronic address: xshi@dhu.edu.cn

   CQM-Centro de Química da Madeira, Universidade da Madeira, Campus da Penteada, 9000-390 Funchal, Portugal

   College of Chemistry, Chemical Engineering and Biotechnology, Donghua University, Shanghai 201620, China

6. Andrij Pich corresponding Aachen DWI-Leibniz-Institute for Interactive Materials e.V Institute of Technical and Macromolecular Chemistry Institute of Technical and Macromolecular Chemistry

   Maastricht University · DWI – Leibniz Institute for Interactive Materials · RWTH Aachen University

   Affiliation as printed

   DWI-Leibniz-Institute for Interactive Materials e.V, 52056 Aachen, Germany; Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, 52074 Aachen, Germany; Aachen Maastricht Institute for Biobased Materials, Maastricht University, 6167 RD Geleen, the Netherlands. Electronic address: pich@dwi.rwth-aachen.de

   Aachen Maastricht Institute for Biobased Materials, Maastricht University, 6167 RD Geleen, the Netherlands

   DWI-Leibniz-Institute for Interactive Materials e.V, 52056 Aachen, Germany

   Institute of Technical and Macromolecular Chemistry, RWTH Aachen University, 52074 Aachen, Germany