Influence of nanoparticles on the brain-to-serum distribution and the metabolism of valproic acid in mice

The suitability of nanoparticles as a drug-carrier system for the antiepile ptic valproic acid has been studied in mice. The aim of the study was to in crease the brain-to-serum ratio of the drug to reduce dose-related side eff ects in the periphery. The influence of nanoparticles on the metabolism of valproic acid was also investigated. The serum kinetics and the brain tissue levels of valproic acid were not al tered by administration with nanoparticles. However, the nanoparticles did inhibit the metabolic degradation of valproic acid via mitochondrial beta-o xidation but did not influence any other metabolic pathway. It can be concluded that nanoparticles loaded with valproic acid may help t o reduce the toxic side effects of valproate therapy, not by reducing the t herapeutically necessary dosage but by inhibition of formation of toxic met abolites. Using their ability to selectively block a pathway nanoparticles may serve as a tool to investigate the metabolic origin of metabolites and their contribution to therapeutic efficacy and side effects.