Surface-anchored microbial enzyme-responsive solid lipid nanoparticles enabling colonic budesonide release for ulcerative colitis treatment

Journal of Nanobiotechnology

Research

Tianhua Zhou¹  Quan Zhou²  Liying Wang³  Yipeng Zhang⁴  Xiangrui Liu⁵  Xuefei Zhou⁶  Zi-Dan Wang⁷  Yi-Xin Guan⁷ 

[1] Department of Cell Biology, Zhejiang University School of Medicine, 310058, Hangzhou, China;Cancer Center, Zhejiang University, 310058, Hangzhou, China;Department of Cell Biology, Zhejiang University School of Medicine, 310058, Hangzhou, China;International Institutes of Medicine, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, 322000, Yiwu, China;Department of General Surgery, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China;Department of Pharmacology and Department of Radiology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China;Zhejiang Key Laboratory of Smart Biomaterials, College of Chemical and Biological Engineering, Zhejiang University, 310027, Hangzhou, China;Innovation Center of Yangtze River Delta, Zhejiang University, 314100, Jiaxing, China;Department of Pharmacology and Department of Radiology of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 310016, Hangzhou, China;Zhejiang Key Laboratory of Smart Biomaterials, College of Chemical and Biological Engineering, Zhejiang University, 310027, Hangzhou, China;Innovation Center of Yangtze River Delta, Zhejiang University, 314100, Jiaxing, China;Cancer Center, Zhejiang University, 310058, Hangzhou, China;International Institutes of Medicine, The Fourth Affiliated Hospital of Zhejiang University School of Medicine, 322000, Yiwu, China;Zhejiang Key Laboratory of Smart Biomaterials, College of Chemical and Biological Engineering, Zhejiang University, 310027, Hangzhou, China;

关键词: Solid lipid nanoparticles;    Ulcerative colitis;    Microbial enzyme;    Colon-targeted oral drug delivery system;    Sodium cellulose sulfate;    Budesonide;   

DOI  :  10.1186/s12951-023-01889-0

 received in 2022-12-26, accepted in 2023-04-10,  发布年份 2023

来源: Springer

【 摘 要 】

Colon-targeted oral drug delivery systems (CDDSs) are desirable for the treatment of ulcerative colitis (UC), which is a disease with high relapse and remission rates associated with immune system inflammation and dysregulation localized within the lining of the large bowel. However, the success of current available approaches used for colon-targeted therapy is limited. Budesonide (BUD) is a corticosteroid drug, and its rectal and oral formulations are used to treat UC, but the inconvenience of rectal administration and the systemic toxicity of oral administration restrict its long-term use. In this study, we designed and prepared colon-targeted solid lipid nanoparticles (SLNs) encapsulating BUD to treat UC by oral administration. A negatively charged surfactant (NaCS-C12) was synthesized to anchor cellulase-responsive layers consisting of polyelectrolyte complexes (PECs) formed by negatively charged NaCS and cationic chitosan onto the SLNs. The release rate and colon-specific release behavior of BUD could be easily modified by regulating the number of coated layers. We found that the two-layer BUD-loaded SLNs (SLN-BUD-2L) with a nanoscale particle size and negative zeta potential showed the designed colon-specific drug release profile in response to localized high cellulase activity. In addition, SLN-BUD-2L exhibited excellent anti-inflammatory activity in a dextran sulfate sodium (DSS)-induced colitis mouse model, suggesting its potential anti-UC applications.

【 授权许可】

CC BY   
© The Author(s) 2023

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