Targeting the ileo-colonic region in inflammatory bowel disease

    Research output: ThesisThesis fully internal (DIV)

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    Abstract

    Inflammatory bowel diseases (IBD) includes Crohn’s disease (CD) and ulcerative colitis (UC). IBD are chronic inflammatory diseases of the gastrointestinal tract (GIT). The inflammation in IBD is generally localized in the GIT. Therefore, topical therapy with anti-inflammatory drugs is the desired therapeutic approach in many cases. However, depending on disease type (UC or CD) and severity, the inflammation may be present throughout the entire GIT, such as the small intestine, ileum, and/or colon. This means that for an effective topical treatment, the drug should be targeted to a given site in the GIT.

    Earlier studies have shown that the ColoPulse coating technology targets oral dosage forms, such as tablet and capsules, to the ileo-colonic region of healthy subjects and CD patients. In this thesis we used this coating to develop three novel tablets that contain topically active anti-inflammatory drugs in view of maximizing the local anti-inflammatory effects in the GIT, whilst minimizing the systemic effects that may result in adverse events. The tablets contained a combination of mesalazine and budesonide (formulation 1), or budesonide only (formulation 2), or the monoclonal antibody infliximab (formulation 3).

    This thesis investigated the drug release characteristics, ileo-colonic targeting performance, and stability of these new formulations. The results showed that these novel formulations are interesting new treatment options for IBD that may be more efficacious than the currently available budesonide and mesalazine formulations since none are optimally suited to treat the ileo-colonic region.
    Ileo-colonic targeting of infliximab has not yet been investigated. However, animal studies as well as small pilot studies suggest that this may be an efficacious treatment option that eliminates the unwanted adverse events that are related to systemic exposure. In a review article we summarize all the available data that support this notion. However, this needs to be investigated in a clinical trial. The study protocol of such a trial is part of this thesis.
    Original languageEnglish
    QualificationDoctor of Philosophy
    Awarding Institution
    • University of Groningen
    Supervisors/Advisors
    • Kosterink, Jos, Supervisor
    • Frijlink, Erik, Supervisor
    • Dijkstra, Gerard, Supervisor
    Award date5-Feb-2021
    Place of Publication[Groningen]
    Publisher
    DOIs
    Publication statusPublished - 2021

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