New strategy of tacrolimus administration in animal model based on tacrolimus-loaded microspheres.
Transpl Immunol
; 36: 9-13, 2016 05.
Article
in En
| MEDLINE
| ID: mdl-27102446
ABSTRACT
New strategies for tacrolimus administration that conserve its immunosuppressive effect but avoiding fluctuations in tacrolimus circulating levels are needed. The aim was to analyze if subcutaneous biodegradable tacrolimus-loaded microspheres injection promoted a significant immunosuppressive response in rats. Rats received two subcutaneous tacrolimus-loaded microspheres injections at different days, the first injection was done at day 0 and the second injection was done 12 days after. Plasma circulating levels of tacrolimus, interleukin-2 (IL-2) and calcineurin phosphatase (PP2B) activity in mononuclear cells were measured. Tacrolimus plasma levels were significantly increased from the day after tacrolimus-loaded microspheres injection and remained increased during 10days. Compared to control, plasma IL-2 levels and PP2B activity in mononuclear cells were significantly decreased during ten days. At day 12, a new subcutaneous injection of tacrolimus-loaded microspheres was performed and two days after injection, tacrolimus plasma levels were again increased and both IL-2 plasma levels and PP2B activity decreased. A single subcutaneous tacrolimus-loaded microspheres injection was enough to reduce tacrolimus-related immunosuppressive parameters. These results open the possibility of new therapeutic strategies to administrate calcineurin inhibitors reducing the variability of their circulating levels related to gastrointestinal drug absorption/metabolism modifications.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Organ Transplantation
/
Tacrolimus
/
Graft Rejection
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Immunosuppressive Agents
/
Microspheres
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Transpl Immunol
Journal subject:
ALERGIA E IMUNOLOGIA
/
TRANSPLANTE
Year:
2016
Document type:
Article
Affiliation country:
Spain