Improved nonclinical pharmacokinetics and biodistribution of a new PPAR pan-agonist and COX inhibitor in nanocapsule formulation.

• Autor(a) principal: Garcia, Giani Martins
• Data de Publicação: 2015
• Outros Autores: Oliveira, Liliam Teixeira, Pitta, Ivan da Rocha, Lima, Maria do Carmo Alves de, Vilela, José Mário Carneiro, Andrade, Margareth Spangler, Parra Abdalla, Dulcinéia Saes, Mosqueira, Vanessa Carla Furtado
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UFOP
• Texto Completo: http://www.repositorio.ufop.br/handle/123456789/5988; https://doi.org/10.1016/j.jconrel.2015.04.033
• topic: Thiazolidinedione; Pharmacokinetics

Wereport the in vitro release profile and comparative pharmacokinetics and biodistribution of a newperoxisome proliferator-activated receptor-γ agonist and cyclooxygenase inhibitor (Lyso-7) free or associated to poly(D,Llactic acid) nanocapsules (NC) after intravenous administration in mice. Lyso-7 pertains to the class of insulinsensitizing agents that shows potential beneficial effects in diabetes therapy. Monodispersed Lyso-7 NC with a mean diameter of 273 nm with high encapsulation efficiency (83%) were obtained. Lyso-7 dissolution rate was reduced (2.6-fold) upon loading in NC. The pharmacokinetic parameters were determined using a noncompartmental approach. In comparison with Lyso-7 in solution, the plasma-AUC increased 14-fold, the mean residence time 2.6-fold and the mean half-life (t1/2) 1.5-fold for Lyso-7-NC; the Lyso-7 plasma clearance, distribution volume and elimination rate were reduced 13, 10 and 1.4 fold, respectively, which indicates higher retention of encapsulated Lyso-7 in the blood compartment. Upon association with NC, organ exposure to Lyso-7 was higher in the heart (3.6-fold), lung (2.8-fold), spleen (2.3-fold), kidney (2-fold) and liver (1.8-fold) compared to Lyso-7 in solution. The analysis of whole data clearly indicates that body exposure to Lyso-7 was enhanced and the general toxicity reduced upon nanoencapsulation, allowing further evaluation of Lyso-7 in nonclinical and clinical studies