Nanoencapsulation of tacrolimus in lipid-core nanocapsules showed similar immunosuppressive activity after oral and intraperitoneal administrations.

Tacrolimus is widely used in the prophylaxis of solid-organ transplant rejection. Several studies have reported that tacrolimus has variable and poor bioavailability after oral administration, apart from adverse effects such as gastrointestinal disorders, hyperglycemia, nephro- and neurotoxicity. The aim of this work was to encapsulate tacrolimus (TAC) in lipid-core nanocapsules (LNC) as an oral strategy to deliver the drug. To validate our hypothesis, the pharmacodynamic effect of TAC-LNC was determined after oral and intraperitoneal (i.p.) administrations to mice. TAC-LNC had z-average diameter of 210 nm (unimodal), and 99.5% of encapsulation efficiency. In vitro sustained release was determined for TAC-LNC fitting an anomalous transport mechanism (n = 0.8). TAC-LNC demonstrated higher immunosuppressive activity after oral and i.p. administrations, when compared to the drug solution. TAC-LNC administered at 6.0 mg kg(-1) day(-1) showed equivalent percent reduction in lymphocyte when both routes of administration were used. After oral administration, drug nanoencapsulation allows reducing the dose by at least 40%. Furthermore, the nanoencapsulation of TAC in lipid-core nanocapsules showed pharmacodynamic effect similar for the oral and the i.p. routes. In conclusion, the lipid-core nanocapsules were able to improve the TAC deliver across the oral absorption barrier.