Nutraceutical emulsion containing valproic acid (NE-VPA): a drug delivery system for reversion of seizures in zebrafish larvae epilepsy model

FEAS, DANIELA AGUSTINA; IGARTÚA, DANIELA EDITH; CALIENNI, MARÍA NATALIA; MARTINEZ, CAROLINA SOLEDAD; PIFANO, MARINA; CHIARAMONI, NADIA SILVIA; DEL VALLE ALONSO, SILVIA; PRIETO, MARÍA JIMENA

Journal of Pharmaceutical Investigation

Springer

Año: 2017

2093-5552

Valproic acid (VPA) is an antiepileptic drug, which is currently used in neurodegenerative diseases. However, a high dose is required to obtain a therapeutic efect. Long-chain polyunsaturated fatty acids (PUFAs), such as omega 3 and omega 6, are eicient complements in treatments for neurological diseases. Previous studies have reported that a dietary supplement containing PUFAs together with the administration of antiepileptic drugs signicantly reduces the frequency of seizures. Based on this, the main goal of this work was to obtain a complex based on VPA encapsulation in an oil/water (o/w) nutraceutical emulsion (NE) enriched with PUFAs for oral administration. Besides, encapsulation of VPA might reduce its dose and increase its therapeutic efect. In order to study its efect, we used a zebraish larvae model of induced epileptiform behavior with the proconvulsant drug pentylenetetrazol (PTZ). Results have shown that when 100 μM VPA and fatty acids were combined in the NE (NE-VPA), the epileptiform behavior of PTZ-treated zebraish larvae decreased signicantly. Additionally, morphological changes, hepato-toxicity, lethality and heart rate were studied. Despite the fact that a high dose of VPA exerted a cardiotoxic efect, this was no longer detected after addition of this drug in the NE. This treatment exerted a signiicant antiepileptic efect and did not result in highly toxic or lethal efects. In order to develop an improved pharmaceutical treatment, and considering that all the components used are FDA approved for consumption, the NE-VPA selected might be easily incorporated into clinical trials.