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Chitosan-based smart microgels for the treatment of inflammatory bowel diseases

More than 5 million people worldwide are affected by inflammatory bowel disease. To enable good treatment, targeted and efficient drug delivery is necessary. In the presented study, a chitosan-based vancomycin loaded microgel was investigated for this purpose.


Xin Li, Laura Hetjens, Nadja Wolter, Helin Li, Xiangyang Shi, Andrij Pich, Charge-reversible and biodegradable chitosan-based microgels for lysozyme-triggered release of vancomycin, Journal of Advanced Research, Volume 43, 2023, Pages 87-96, ISSN 2090-1232,

Inflammatory bowel disease (IBD) affects more than 5 million people worldwide with a rising trend. The chronic inflammatory syndrome can lead to intestinal obstructions, chronic diarrhea or even colon cancer. Conventionally, IBDs are treated with antibiotics in combination with immunosuppressants. However, these therapies have so far been poorly targeted and the active ingredients very highly dosed to produce the desired effect. As a result, severe side effects and drug resistance are possible. Oral administration of drugs against IBD leads to fewer side effects and higher drug efficiency compared to e.g. rectal administration. However, drugs must be able to survive transport through gastric acid. To enable appropriate treatment of IBDs, drug delivery systems with sufficient gastric acid resistance and controllable drug release are needed.

One solution for this may be smart microgels (MG), these have adjustable particle size and excellent loading capacities, are able to respond to stimuli and can act as a shell to improve tolerance in acidic environments. Chitosan (CH) is considered a promising material in this regard. It is FDA approved, well researched in controlled release and has exceptional antibacterial and anti-inflammatory properties due to its cationic nature. It also has good mucoadhesive properties. In previous studies, drug release was often regulated by environmental pH, but specific regulation for intestinal diseases to enable precise and controllable release has been lacking. Recent studies had shown that intestinal pathogens disrupt cellular functions, resulting in increased secretion of lysozyme.

Therefore, in the presented study, a vancomycin loaded chitosan-polyaniline microgel (CH-PANI MG) was developed for lysozyme-controlled drug release. For the preparation, aniline was dropped on CH (190-310 kDa) and then crosslinked with glutaraldehyde (GA) and loaded with vancomycin (VM). In addition to the physiochemical properties of the microgel, the drug release was investigated on a model as well as the antibacterial properties against S. aureus.


  • Successful synthesis of CH-PANI MGs that exhibited charge reversible behavior (positive to negative charges) upon treatment with NaCl
  • High loading efficiency with the cationic VM for the negatively charged N-CH-PANI MG (182.6 mg/mg or 91.3%) in contrast to the positively charged N-CH-PANI MG (18.2%)
  • Good biodegradation of N-CH-PANI MGs by the lysozyme, as well as controlled release of VM
  • Model digestive tract: no change in morphology of N-CH-PANI MGs at pH 3 (pH of gastric acid) and pH 6.8 (healthy intestine), while the latter completely decomposed at pH 6.8 + lysozyme
  • At pH 6.8 + lysozyme, a VM release of 76.9% was observed within a short time, only a small release in the absence of lysozyme (16.8%)
  • Good biocompatibility of N-CH-PANI MGs with cell viability above 86.1 % of Caco-2 cells
  • Good antibacterial effect against S. aureus of N-CH-PANI@VM MGs at pH 6.8 in the presence of lysozyme at already low levels

Conclusions: In the presented study, a CH-based charge reversible microgel was successfully synthesized that can be loaded with VM via electrostatic interactions. Besides the good gastric acid resistance of the microgel, VM can be specifically released by lysozyme into the inflamed intestinal region. Moreover, good antibacterial activity was observed even at low concentrations. Overall, the formulation showed great potential for oral drug delivery in the treatment of IBD.

Link to article: Charge-reversible and biodegradable chitosan-based microgels for lysozyme-triggered release of vancomycin - ScienceDirect

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drug delivery, chitosan, antimicrobial, microfluidic

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