RESUMO
Core-shell nanoparticles (CSNPs) were developed to get over therapeutic amount of kynurenic acid (KYNA) across the blood-brain barrier (BBB). Bovine serum albumin (BSA) was used as core for encapsulation of KYNA and the BSA/KYNA composite was finally encapsulated by poly(allylamine) hydrochloride (PAH) polymer as shell. In the interest of the optimization of the synthesis the BSA and KYNA interaction was studied by two-dimensional surface plasmon resonance (SPR) technique as well. The average size of d~100 nm was proven by dynamic light scattering (DLS) and transmission electron microscopy (TEM), while the structure of the composites was characterized by fluorescence (FL) and circular dichroism (CD) spectroscopy. The in vitro release properties of KYNA were investigated by a vertical diffusion cell at 25.0 °C and 37.5 °C and the kinetic of the release were discussed. The penetration capacity of the NPs into the central nervous system (CNS) was tested by an in vitro BBB model. The results demonstrated that the encapsulated KYNA had significantly higher permeability compared to free KYNA molecules. In the neurobiological serial of in vivo experiments the effects of peripherally administered KYNA with CSNPs were studied in comparison with untreated KYNA. These results clearly proved that KYNA in the CSNPs, administrated peripherally is suitable to cross the BBB and to induce electrophysiological effects within the CNS. As the neuroprotective properties of KYNA nowadays are proven, the importance of the results is obvious.
Assuntos
Barreira Hematoencefálica/metabolismo , Portadores de Fármacos/administração & dosagem , Ácido Cinurênico/administração & dosagem , Nanopartículas/administração & dosagem , Poliaminas/administração & dosagem , Soroalbumina Bovina/administração & dosagem , Animais , Dicroísmo Circular , Técnicas de Cocultura , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Células Endoteliais/metabolismo , Ácido Cinurênico/química , Ácido Cinurênico/farmacocinética , Nanopartículas/química , Neuroglia/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/farmacocinética , Pericitos/metabolismo , Poliaminas/química , Poliaminas/farmacocinética , Ratos Wistar , Soroalbumina Bovina/química , Soroalbumina Bovina/farmacocinética , Espectrometria de Fluorescência , Ressonância de Plasmônio de SuperfícieRESUMO
Since most of the proteinogenic alpha-amino acids contain a chiral carbon atom, the stereoisomers of both these amino acids and the peptides in which they are to be found may possess differences in biological activity in living systems. The important analytical task of the separation of optical isomers is achieved mainly by chromatographic methods. This special review surveys direct and indirect HPLC separations of biologically important, small epimeric peptides and their L, D-amino acid content.