4.2 Article

Colon-Specific Delivery of Bioactive Agents Using Genipin-Cross-Linked Chitosan Coated Microcontainers

期刊

ACS APPLIED BIO MATERIALS
卷 4, 期 1, 页码 752-762

出版社

AMER CHEMICAL SOC
DOI: 10.1021/acsabm.0c01333

关键词

chitosan; genipin; local delivery; enzyme-triggered release; microdevices; Lactobacillus rhamnosus GG

资金

  1. Novo Nordisk Foundation as a part of the project MIMIO [NNF17OC0026910]
  2. Danish National Research Foundation [DNRF122]
  3. Villum Foundation as a part of the Center for Intelligent Drug Delivery and Sensing Using Microcontainers and Nanomechanics (IDUN) [9301]

向作者/读者索取更多资源

This study focuses on the proof of concept for engineered delivery of probiotics using micrometer-sized polymeric containers, and demonstrates that chitosan-genipin coated microcontainers enable effective local delivery in the cecum and colon.
Oral administration of probiotics is beneficial for restoring the intestinal microbial balance and for the treatment of gastrointestinal (GI) tract-related disorders. In the current era characterized by the development of next-generation probiotic microorganisms, which are typically less robust toward environmental challenges than the classically applied lactic acid producing probiotics, we anticipate a need for delivery of live organisms directly to the site where they need to colonize. Here, we thus present, for the first time, a proof of concept for using micrometersized polymeric containers, for the engineered delivery of probiotics, using spray dried Lactobacillus rhamnosus GG (LGG), as a model probiotic microorganism. To achieve colon-specific delivery, microcontainers are loaded with LGG and sealed with an enzyme-sensitive coating. A genipincross-linked chitosan coating is developed that (i) is stable at gastric and intestinal pH; (ii) has tunable swelling; and (iii) is degradable by the colon-specific bacterial enzymes. The chitosan-genipin coated microcontainers are evaluated in vitro, ex vivo, as well as in vivo in a rat model. Our results confirm that the genipin-cross-linked chitosan coating enables an effective local delivery in the cecum and colon without any premature release in the small intestine. Our findings suggest that the integration of modified polysaccharides with ingestible microdevices has great potential for controlled and site-specific delivery of live microorganisms.

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