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

Khorshid Kamguyan*, Anders Meyer Torp, Juliane Fjelrad Christfort, Priscila Guerra, Tine Rask Licht, Line Hagner Nielsen, Kinga Zor, Anja Boisen

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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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 micrometer-sized 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 genipin-cross-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.

Original languageEnglish
JournalACS Applied Bio Materials
Issue number1
Pages (from-to)752–762
Publication statusPublished - 2021


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


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