Targeting of the kynurenic acid across the blood-brain barrier by core-shell nanoparticles

N. Varga, E. Csapó, Z. Majláth, I. Ilisz, I. A. Krizbai, I. Wilhelm, L. Knapp, J. Toldi, L. Vécsei, I. Dékány

Research output: Article

20 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)67-74
Number of pages8
JournalEuropean Journal of Pharmaceutical Sciences
Volume86
DOIs
Publication statusPublished - ápr. 30 2016

ASJC Scopus subject areas

  • Pharmaceutical Science

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