The efficacy of inhaled nanoparticle tacrolimus in preventing rejection in an orthotopic rat lung transplant model.

Abstract

The immunosuppressive efficacy of inhaled nanoparticle tacrolimus was compared with systemic tacrolimus in a rodent allogeneic lung transplant model. Sixteen rats underwent allogeneic left orthotopic lung transplantation and were divided into 3 treatment groups: (1) inhaled nanoparticle tacrolimus: 6.4 mg tacrolimus/6.4 mg lactose twice per day; (2) intramuscular tacrolimus: 1 mg/kg tacrolimus once per day; and (3) inhaled lactose: 6.4 mg of lactose twice per day. Five days after transplant, the rats were necropsied and underwent histologic rejection grading and cytokine analysis. Trough levels of tacrolimus were measured in allograft, blood, and kidney. Both intramuscular (n = 6) and nanoparticle tacrolimus (n = 6) rats displayed lower histologic grades of rejection (mean scores 3.4 ± 0.6 and 4.6 ± 0.9, respectively) when compared with lactose rats (n = 4) (mean score 11.38 ± 0.5, P = .07). Systemic tacrolimus trough levels (median) were lower in nanoparticle tacrolimus-treated rats versus intramuscular-treated rats (29.2 vs 118.6 ng/g; P < .001 in kidney, and 1.5 vs 4.8 ng/mL; P = .01 in blood). Inhaled nanoparticle tacrolimus provided similar efficacy in preventing acute rejection when compared with systemic tacrolimus while maintaining lower systemic levels.