Development of an oral drug delivery system targeting immune-regulating cells in experimental inflammatory bowel disease: A new therapeutic strategy

Several studies have indicated the involvement of macrophages and dendritic cells in active inflammatory bowel disease (IBD). Manipulation of these ce lls is considered a very important therapeutic strategy for patients with I BD. We evaluated the effect of a new drug delivery system targeting microfo ld cells and macrophages with poly( DL-lactic acid) microspheres containing dexamethasone (Dx). Colitis was induced in BALB/c mice by 5% dextran sodiu m sulfate. Dx microspheres (n = 10) and only Dx (n = 10) were orally admini stered to dextran sodium sulfate-treated mice. Thereafter, serum levels and tissue distributions of Dx were investigated. To estimate the efficacy of this drug delivery system, we measured the histological score, myeloperoxid ase activity and nitric oxide production, and gene expressions of tumor nec rosis factor-alpha, interleukin-1 beta, and interferon-gamma in the colonic tissue. Serum Dx levels were not increased after oral administration of Dx microspheres. The tissue distribution of microspheres containing I-125-lab eled Dx in inflamed colon was significantly higher than in other organs. Th e histological score, myeloperoxidase activity, and nitric oxide production of the group treated with Dx microspheres were significantly lower than of those treated with Dx alone. Gene expressions of tumor necrosis factor-alp ha, interleukin-1 beta, and interferon-gamma were down-regulated in mice tr eated with Dx microspheres. Microspheres containing glucocorticoids such as Dx, which target microfold cells and macrophages, can facilitate mucosal r epair in experimental colitis and could be an ideal agent for treatment of human IBD.