Intestinal drug delivery systems with biodegradable microspheres targeting mucosal immune-regulating cells for chronic inflammatory colitis.
We developed two kinds of delivery systems targeting mucosal immune regulating cells with poly (D,L-lactic acid) microspheres containing dexamethasone and dichloromethylene diphosphonate, and gelatine microspheres containing interleukin-10. To estimate the efficacy of these drug delivery systems, we studied the effects on experimental colitis induced by dextran sodium sulfate, 2,4,6-trinitrobenzene sulfonic acid, and interleukin-10-deficient mice. Intestinal administration of these microspheres significantly improved colitis with decreased histological score, myeloperoxidase activity, and nitric oxide production compared with mice treated with free agents. Gene expressions of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma were down-regulated in treated animals. Serum Dx, IL-10 levels, and systemic macrophages were unchanged after treatment. Our findings suggest that local macrophages in the intestine play a critical role in the initiation of chronic colitis in the animal model of inflammatory bowel disease (IBD). Intestinal drug delivery systems with biodegradable microspheres targeting mucosal immune-regulating cells may become a therapeutic approach to human IBD.
Okazaki
Kazuichi
K
Division of Gastroenterology and Endoscopic Medicine, Graduate School of Kyoto University, 54 Shogoinkawara-cho, Sakyoku, Kyoto 606-8507, Japan.
Nakase
Hiroshi
H
Watanabe
Norihiko
N
Tabata
Yasuhiko
Y
Ikada
Yoshito
Y
Chiba
Tsutomu
T
D000818:Animals; D001682:Biological Availability; D002908:Chronic Disease; D016207:Cytokines / Q000032:analysis / Q000378:metabolism*; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005260:Female; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy*; D016753:Interleukin-10 / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000187:drug effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008863:Microspheres; D011336:Probability; D011379:Prognosis; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
D016207:Cytokines; D016753:Interleukin-10; D003907:Dexamethasone