RRC ID 17631
Author Fukata N, Uchida K, Kusuda T, Koyabu M, Miyoshi H, Fukui T, Matsushita M, Nishio A, Tabata Y, Okazaki K.
Title The effective therapy of cyclosporine A with drug delivery system in experimental colitis.
Journal J Drug Target
Abstract Cyclosporine A (CyA) is a useful immunosuppressive agent for steroid-dependent or steroid-refractory ulcerative colitis. However, side effects have been reported in clinical trials of ulcerative colitis treated with CyA. Biodegradable microspheres (MS) have been investigated as drug delivery system. We evaluated the effect of a drug delivery system with poly(d,l-lactic acid)-MS containing CyA. Colitis was induced in C57BL/6 mice by 3% dextran sulfate sodium (DSS). Mice with DSS-induced colitis were treated with oral administration of CyA or CyA-MS: CyA (0.2 mg/kg/day)-MS; CyA (2 mg/kg/kg)-MS). Serum levels of CyA were significantly less elevated after oral administration of CyA (2 mg/kg/day)-MS compared with CyA (2 mg/kg/day) (CyA (2 mg/kg/day), 44.7 ± 0.8 ng/ml; CyA (2 mg/kg/day)-MS, 7.7 ± 1.3 ng/ml). The body weight at day 10 was significantly recovered in the mice treated with CyA (0.2 mg/kg/day)-MS and CyA (2 mg/kg/day)-MS compared with CyA (0). The histological score and myeloperoxidase activity in the mice treated with CyA-MS was significantly lower than CyA (0). Gene expressions of interleukin-1β (IL-1β), IL-6, and CXCL1 in the mice treated with CyA (0.2 mg/kg/day)-MS and CyA (2 mg/kg/day)-MS were downregulated compared with CyA (0)-MS. CyA-MS might be possible to treat ulcerative colitis effectively by decreasing the total dosage without the elevation of the serum level or the side effects of CyA.
Volume 19(6)
Pages 458-67
Published 2011-7
DOI 10.3109/1061186X.2010.511224
PMID 20804404
MeSH Administration, Oral Animals Biocompatible Materials / chemistry Cell Line Colitis / drug therapy* Colitis / immunology Colitis / pathology Cyclosporine / administration & dosage Cyclosporine / pharmacokinetics Cyclosporine / therapeutic use* Cytokines / genetics Cytokines / immunology Disease Models, Animal Drug Carriers / chemistry Drug Delivery Systems / methods* Gene Expression Immunosuppressive Agents / administration & dosage Immunosuppressive Agents / pharmacokinetics Immunosuppressive Agents / therapeutic use* Lactic Acid / chemistry Macrophages / drug effects Macrophages / immunology Macrophages / metabolism Mice Mice, Inbred C57BL Microspheres Polyesters Polymers / chemistry Tissue Distribution
IF 3.277
Times Cited 5
Human and Animal Cells RAW 264 (RCB0535)