DEVELOPMENT AND IN VITRO CHARACTERIZATION OF NANOSTRUCTURED LIPID CARRIERS WITH CANNABIDIOL AND STIRIPENTOL AS A POTENTIAL THERAPEUTIC STRATEGY FOR DRAVET SYNDROME

SCIOLI-MONTOTO, SEBASTIÁN; LIBOS, EDUARDO MARTÍN; CHAIN, CECILIA YAMIL; ISLAN, GERMÁN A; TALEVI, ALAN; RUIZ, MARÍA ESPERANZA

Encuentro; REUNIÓN CONJUNTA SAIC SAFIS ALACF 2024; 2024

SAIC, SAFIS, ALACF

Dravet syndrome is a severe drug-resistance type of epilepsy that can occur in the first year of life in previously healthy children. One of the main problems in the treatment of this syndrome is that drugsacting on sodium channels (phenytoin, carbamazepine, oxcarbazepine, lamotrigine, etc.) cannot be used since they exacerbate seizures in these patients. Recently, only Stiripentol (STP) has emerged as a specific treatment for this syndrome. However, it has a very low and variable bioavailability, and a high plasma protein binding which could lead to interactions. In recent years cannabidiol (CBD) has shown certain effectivity over refractory epilepsy. Nevertheless, CBD has a low water solubility, low bioavailability and a variable pharmacokinetic, needing high doses to achieve a therapeutic effect. A strategy capable of overcoming both drugs problems is their incorporation within nanostructured lipid carriers, capable of crossing different biological barriers and thus allowing a better arrival of these drugs to their site of action, improving their bioavailabilityand decreasing their adverse effects. The objectives of this work were to develop and characterize, in terms of particle size, Z potential, polydispersity index (PdI) and percentual entrapment efficiency(%EE), nanostructured lipid carriers containing STP and CBD and to study their release kinetics. Nanoparticles were prepared using homogenization by ultrasonication technique. Particle size, Z potential and PdI were measured using a Z-sizer, while in vitro release study was carried out by the dialysis bag method. The developed formulation averaged particle sizes, PdI and Z potential between 174 to 190 nm, 0.184 to 0.250 and -11.63 to -6.60 mV, respectively and also showed a high %EE (over 99%). On the other side, drugs showed a prolonged release for up to 24 hs. Although many more studies are needed, these nanoparticles containing STP and CBD are a promising tool for the treatment of Dravet syndrome.