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Chitosan and chitosan-based particle systems containing a bioactive fish peptide in the abatement of Escherichia coli related infections in the small intestine

Publikation: Bog/antologi/afhandling/rapportPh.d.-afhandling

  • Stefanie Bechstein, Danmark
Escherichia coli infections, especially of the intestinal tract, belong to the most neglected diseases in scientific research. However, every year they are causative for more than over 1.000.000 deaths related to diarrhea and long-term consequences with not only developing countries being concerned, but also industrialised nations. Though, triggering strains as well as their properties differ from country to country. While developing countries suffer primarily from enteropathogenic E.coli (EPEC) infections and also often from enterotoxigenic E.coli (ETEC) infections, the industrialized world is more seriously affected by ETEC and enterohemorrhagic E.coli (EHEC). To date, there is no satisfying treatment option as the normally applied antibiotics often lead to problems like resistance development and toxic side effects for the patient. Newer approaches are the development of vaccines which though can only be utilized as a preventive measurement but not when the infection has occured. The development is complicated by the variety of strains that exist since a vaccine has to be designed rather specifically.
Therefore a remedy is needed that is not strain specific and does not harm the host system. Additionally, it should have preventive effects and should also be able to eradicate an already established infection or biofilm. Hence, chitosan appears to be a good choice. Chitosan is a natural polymer that is commonly found in crustacean shells and exhibits antibacterial activity. The effect is supposably mediated by the positive overall charge that can disturb the bacterial membrane system.
Here, it was shown that CS can interact with bacteria leading to their aggregation and subsequently also bacterial death. Moreover, it was revealed that CS solutions are able to disrupt bacterial organization on a surface, implying an application in biofilm treatments.
Additionally, a fish peptide called piscidin 1 was employed which also harbors antibacterial activity. In this work, a combination of both was supposed to be incorporated into a particle system to make the peptide more compliant with oral delivery and to increase the availability of drug molecule on the site of action. Different particle systems were prepared by spray drying CS-TPP and by double-emulsion evaporation or nanoprecipitation (PLGA). All prepared particle systems were thoroughly chracterized and tested on bacterial suspensions as well as a Caco-2-cell EPEC assay. Moreover, the PLGA particles were CS-coated to ensure interactions with the bacteria. In this study it could be shown that release assay samples of some particle systems were able to confer antibacterial activity. However, most of the particle release samples appeared inactive probably due to a high particle stability, suggesting that further modifications and improvements of the systems have to be undertaken. Coated particles were shown to interact with the bacteria sufficiently and the CS coat was able to initiate bacterial aggregation. Furthermore, chitosan and CS-based particles were found to have a protective effect on Caco-2-cells due to their ability to disrupt bacterial organization and therefore minimize the harmful effects of the bacteria upon cells. Best results were shown for pure CS solution and spray-dried particles.
Though, it could clearly be seen that more research and improvements are necessary to make the particle systems applicable in daily life, results appear promising with respect to biofilm treatments and for the eradication of already established bacterial infections.
ForlagAarhus University, Faculty of Science and Technology
Antal sider194
Rekvirerende organGraduate School of Science and Technology
StatusUdgivet - 2012

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