title: Nanoencapsulation of tacrolimus in lipid-core nanocapsules showed similar immunosuppressive activity after oral and intraperitoneal administrations.
abstract: 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.
authors.forename: R B
authors.initials: RB
authors.lastname: Friedrich
authors.forename: F A
authors.initials: FA
authors.lastname: Dimer
authors.forename: S S
authors.initials: SS
authors.lastname: Guterres
authors.forename: R C R
authors.initials: RC
authors.lastname: Beck
authors.forename: A R
authors.initials: AR
authors.lastname: Pohlmann
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D007263:Infusions, Parenteral; D008055:Lipids / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D008214:Lymphocytes / Q000166:cytology / Q000187:drug effects; D008297:Male; D051379:Mice; D053769:Nanocapsules / Q000008:administration & dosage / Q000737:chemistry*; D016559:Tacrolimus / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D007166:Immunosuppressive Agents; D008055:Lipids; D053769:Nanocapsules; D016559:Tacrolimus