Preparation and properties of nanoscale containers for biomedical application in drug delivery: preliminary studies with kynurenic acid

Abstract

The main purpose of this study was to facilitate the delivery of kynurenic acid (KYNA) across the blood-brain barrier (BBB) by applying micelles as nanoscale containers. Non-ionic amphiphilic molecules were used for preparation of spherical micelles for delivery of kynurenic acid in aqueous solution in physiological condition. It was established that Triton X 100 and Lutensol AP 20 non-ionic surfactants are able to produce stable nanocontainers for delivery of kynurenic acid molecules. The incorporation of KYNA molecules was investigated by dynamic light scattering and the size of micelles were calculated between 5 and 10 nm in 150 mM NaCl and pH 7.5-7.6 solutions. Encapsulated kynurenic acid showed a significantly higher blood-brain barrier permeability compared with non-encapsulated kynurenic acid. The in vivo experiments showed that the encapsulated kynurenic acid is able to display effects within the central nervous system, even after its peripheral administration.

Evaluation of solubility enhancement, antioxidant activity, and cytotoxicity studies of kynurenic acid loaded cyclodextrin nanosponge

“…The decreased concentration of KYNA in the CNS is associated with several neurological disorders such as Parkinson's disease, multiple sclerosis and Huntington's disease (Schwarcz, Bruno, Muchowski, & Wu, 2013;Stone & Connick, 1985). However, low aqueous solubility and limited blood-brain barrier (BBB) permeability limits its therapeutic application (Hornok et al, 2012;Varga et al, 2016). Moreover, kynurenic acid itself has the ability to cross the blood-brain barrier (BBB) to a limited extent and accumulates in the brain on systemic administration (Stone, 2001).…”

Kinureninek és gyógyszerkutatás

“…A micellába zárt KYNA a hatóanyag koncentrációjának szinten tartására adhat megoldást az agyban. In vivo vizsgálatok során jelentős KYNA jutott a központi idegrendszerbe, míg a micella nélküli KYNA nem okozott változást [40]. A KYNA becsomagolása lehetőséget nyújthat a KYNA kapszulázására.…”

Brain Aging and Disorders of the Central Nervous System: Kynurenines and Drug Metabolism

“…Through the use of these carriers, therapeutic drug levels may be achieved in the brain, even for drugs which would otherwise not reach the CNS. This approach has been investigated to facilitate KYNA delivery into the brain by preparing micelles as nanoscale containers 261 : non-ionic surfactants were used to deliver KYNA, the central effects of which were proved in in vivo studies after peripheral administration too.…”