Drug Targeting in IBD Treatment – Existing and New Approaches

Abstract

Recent advances in understanding of inflammatory bowel diseases (IBD) pathogenesis, despite the questions remaining still unanswered, have led to improved approaches in ulcerative colitis (UC) and Crohn`s disease (CD) treatment. In depth investigation of immunopathology of IBD and mucosal inflammation enabled the identification of new strategies for drug targeting, new points of therapeutic attack, cytokine based therapies and new therapeutic agents. Further understanding of the genetic background of this disease will enable discovery of potential gene therapy target molecules related to chronic intestinal inflammation, like new therapeutic targets in IBD. There is a vast body of information and research associated with current medical treatments, their undesirable effects and limited efficacy. Different drug delivery strategies were employed to overcome limited performance of conventional IBD therapy and many more will be designed to enable safe and efficacious delivery of newly developed therapeutic agents. Both diseases, UC and CD involve different parts of the gastrointestinal (GI) system. CD may involve any part of the GI tract, although most commonly the terminal ileum and colon, while UC usually involves only the colon and always extends proximally from the rectum. T helper 1 (Th1) stimulated immune dysregulation is characteristic for CD while T helper 2 (Th2) stimulated immune dysregulation causes inflammatory mediatory imbalance characteristic for UC (Bouma & Strober, 2003; Hedley, 2000; Sands, 2007; Sellin, 2005). Treatment of UC and CD varies depending on subtype and severity, but significant overlap is seen. The most common therapeutic agents for IBD, aminosalycilates and corticosteroids, have been incorporated into different dosage forms and drug delivery systems (DDS) in order to accomplish successful topical delivery of these agents at the site of inflammation (in CD terminal ileum, or colon, the site of inflammation for both subtypes) (Green et al., 2002; Haddish-Berhane et al., 2007; Sands, 2007). The most critical step in the development of a reliable DDS for IBD treatment is to achieve improved localization and controlled release of the active substance at the site of inflammation, minimizing the premature release and subsequent absorption in the blood stream. However, the main disadvantage of today’s therapy and DDS for management of IBD is the inability to target the drug directly to the site of action (inflammation) and/or to maintain high local concentration. In addition to poor localization extensive metabolism at the level of the epithelial cells of the intestinal wall