title: Targeting of the kynurenic acid across the blood-brain barrier by core-shell nanoparticles.
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.
authors.affiliation: MTA-SZTE Supramolecular and Nanostructured Materials Research Group, Department of Medical Chemistry, Faculty of Medicine, University of Szeged, H-6720 Dóm tér 8, Szeged, Hungary.
authors.forename: N
authors.initials: N
authors.lastname: Varga
authors.affiliation: MTA-SZTE Supramolecular and Nanostructured Materials Research Group, Department of Medical Chemistry, Faculty of Medicine, University of Szeged, H-6720 Dóm tér 8, Szeged, Hungary.
authors.forename: E
authors.initials: E
authors.lastname: Csapó
authors.affiliation: Department of Neurology, University of Szeged, H-6725 Semmelweis u. 6, Szeged, Hungary.
authors.forename: Z
authors.initials: Z
authors.lastname: Majláth
authors.affiliation: Department of Inorganic and Analytical Chemistry, University of Szeged, H-6720 Dóm tér 7, Szeged, Hungary.
authors.forename: I
authors.initials: I
authors.lastname: Ilisz
authors.affiliation: Institute of Biophysics, Biological Research Centre of the Hungarian Academy of Sciences, H-6726 Temesvári krt. 62, Szeged, Hungary.
authors.forename: I A
authors.initials: IA
authors.lastname: Krizbai
authors.affiliation: Institute of Biophysics, Biological Research Centre of the Hungarian Academy of Sciences, H-6726 Temesvári krt. 62, Szeged, Hungary.
authors.forename: I
authors.initials: I
authors.lastname: Wilhelm
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, University of Szeged, H-6726 Közép fasor 52, Szeged, Hungary.
authors.forename: L
authors.initials: L
authors.lastname: Knapp
authors.affiliation: Department of Physiology, Anatomy and Neuroscience, University of Szeged, H-6726 Közép fasor 52, Szeged, Hungary; MTA-SZTE Neuroscience Research Group, H-6725 Semmelweis u. 6, Szeged, Hungary.
authors.forename: J
authors.initials: J
authors.lastname: Toldi
authors.affiliation: Department of Neurology, University of Szeged, H-6725 Semmelweis u. 6, Szeged, Hungary; Department of Physiology, Anatomy and Neuroscience, University of Szeged, H-6726 Közép fasor 52, Szeged, Hungary.
authors.forename: L
authors.initials: L
authors.lastname: Vécsei
authors.affiliation: MTA-SZTE Supramolecular and Nanostructured Materials Research Group, Department of Medical Chemistry, Faculty of Medicine, University of Szeged, H-6720 Dóm tér 8, Szeged, Hungary. Electronic address: i.dekany@chem.u-szeged.hu.
authors.forename: I
authors.initials: I
authors.lastname: Dékány
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002942:Circular Dichroism; D018920:Coculture Techniques; D004337:Drug Carriers / Q000008:administration & dosage* / Q000737:chemistry; D065546:Drug Liberation; D042783:Endothelial Cells / Q000378:metabolism; D007736:Kynurenic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D053758:Nanoparticles / Q000008:administration & dosage* / Q000737:chemistry; D009457:Neuroglia / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D020286:Pericytes / Q000378:metabolism; D011073:Polyamines / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D017208:Rats, Wistar; D012710:Serum Albumin, Bovine / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics; D013050:Spectrometry, Fluorescence; D020349:Surface Plasmon Resonance
chemical_list: D004337:Drug Carriers; D018696:Neuroprotective Agents; D011073:Polyamines; D012710:Serum Albumin, Bovine; C063994:polyallylamine; D007736:Kynurenic Acid
keywords: BBB model; Core-shell nanoparticles; Kynurenic acid; Release; Release kinetic