Drug delivery system using microspheres that contain tacrolimus in porcine small bowel transplantation.
Rejection remains a major barrier to successful bowel transplantation, in spite of improved immunosuppressive techniques. Therefore, new, more effective, immunosuppressants, with fewer side effects, are needed. Biodegradable microspheres containing tacrolimus (FK506) were used in an experimental porcine small bowel transplantation. Twenty pigs underwent transplantation and were divided into four groups according to the immunosuppressive regimen. Group A (n = 5): no immunosuppression; group B (n = 6): 0.2 mg/kg per day of FK506; group C (n = 3): 1.0 mg/kg per day of FK506; group D (n = 6): 0.04 mg/kg per day of FK506 contained in biodegradable microspheres. Rejection was diagnosed macroscopically by endoscopic examination and histologically by biopsy specimen analysis. The mean survival time and standard deviation (SD) were 8.8+/-3.5, 11.0+/-1.4, 9.7+/-2.5 and 28.6+/-22.5 days for groups A, B, C, and D, respectively, with a statistically significant difference found between group D, on the one hand, and groups A, B and C, on the other. The mean trough blood concentration of FK506 was 10.5+/-2.2, 27.9+/-6.0 and 10.5+/-3.5 ng/ml in groups B, C and D, respectively. In groups A and B, all pigs died of rejection, without infection. In group C, all died of infection, without rejection. In contrast, none of the pigs in group D developed rejection or infection. Our results clearly show that the drug delivery system using biodegradable microspheres that contain FK506 is effective for controlling rejection with fewer side effects in the porcine small bowel transplantation.
Eshita
Yukitsuna
Y
Department of Transplantation and Immunology, Faculty of Medicine, Kyoto University, 54 Kawara-cho, Shogoin, 606-8507, Kyoto, Japan. eshita@clin.medic.mie-u.ac.jp
Uemoto
Shinji
S
Tabata
Yasuhiko
Y
Sakamoto
Seisuke
S
Egawa
Hiroto
H
Hashida
Tohru
T
Inui
Kenichi
K
Tanaka
Koichi
K
D000818:Animals; D021461:Animals, Outbred Strains; D002423:Cause of Death; D016503:Drug Delivery Systems / Q000379:methods*; D006084:Graft Rejection / Q000188:drug therapy* / Q000401:mortality; D007166:Immunosuppressive Agents / Q000097:blood / Q000493:pharmacokinetics*; D007421:Intestine, Small / Q000637:transplantation*; D008863:Microspheres; D013552:Swine; D016559:Tacrolimus / Q000097:blood / Q000493:pharmacokinetics*; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D016559:Tacrolimus