RRC ID |
17631
|
著者 |
Fukata N, Uchida K, Kusuda T, Koyabu M, Miyoshi H, Fukui T, Matsushita M, Nishio A, Tabata Y, Okazaki K.
|
タイトル |
The effective therapy of cyclosporine A with drug delivery system in experimental colitis.
|
ジャーナル |
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.
|
巻・号 |
19(6)
|
ページ |
458-67
|
公開日 |
2011-7-1
|
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 |
3.38
|
引用数 |
9
|
WOS 分野
|
PHARMACOLOGY & PHARMACY
|
リソース情報 |
ヒト・動物細胞 |
RAW 264(RCB0535) |