title: Biodegradable microsphere-loaded tacrolimus enhanced the effect on mice islet allograft and reduced the adverse effect on insulin secretion.
abstract: The adverse effects of tacrolimus have limited the use of this potent immunosuppressive drug in clinical transplantation. To improve the therapeutic effects, we developed a new type of tacrolimus with biodegradable microsphere technology and examined the immunosuppressive effects on allogeneic islet transplantation and the side-effects on insulin secretion in vivo. With a single subcutaneous injection, mouse blood concentrations of tacrolimus (M-FK) carried in biodegradable microspheres remained flat for 2 weeks (only 10 h for conventional tacrolimus). A single subcutaneous administration of 20 mg/kg of M-FK significantly prolonged the survival of islet allografts (MST = 28 days) compared with the control group (MST = 10 days). Series administration of 10 mg/kg of M-FK at 7-day intervals markedly prolonged the survival of islet grafts, and resulted in 60% allograft acceptance. In mice with syngeneic islet transplantations, a single administration of 30 mg/kg of tacrolimus inhibited insulin secretion, whereas a single administration of an equal dosage of M-FK did not. The results suggested that M-FK enhanced the immunosuppressive effects on islet allograft rejection more effectively with reduced side-effects on insulin secretion.
authors.affiliation: Laboratory of Transplantation Immunology, Department of Innovative Surgery, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Quanxing
authors.initials: Q
authors.lastname: Wang
authors.forename: Takeji
authors.initials: T
authors.lastname: Uno
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hara
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Kitazawa
authors.forename: Fei-Zhou
authors.initials: FZ
authors.lastname: Lu
authors.forename: Naoko
authors.initials: N
authors.lastname: Funeshima
authors.forename: Masayuki
authors.initials: M
authors.lastname: Fujino
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Takenaka
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kawashima
authors.forename: Xiao-Kang
authors.initials: XK
authors.lastname: Li
mesh_terms: D000818:Animals; D005260:Female; D006085:Graft Survival / Q000187:drug effects*; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D051379:Mice; D008863:Microspheres; D016559:Tacrolimus / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood; D013997:Time Factors
chemical_list: D007166:Immunosuppressive Agents; D007328:Insulin; D016559:Tacrolimus