Lipid nanoparticles for the delivery of phenobarbital: design, optimization, characterization and in vivo evaluation

SCIOLI MONTOTO, S.; SBARAGLINI, M.L.; CISNEROS, J.S.; CHAIN, C.Y.; TALEVI, A.; ALVAREZ, V.A.; CASTRO, G.R.; RUIZ, M.E.

Rosario

Congreso; 6ª Reunión Internacional de Ciencias Farmacéuticas. RICiFa 2020+1; 2021

Universidades Nacionales de Rosario y de Córdoba

Epilepsy is one of themost common neurological disorders, affecting around 50 million peopleworldwide. Due to restrictions imposed by the blood brain barrier, high dosesof antiepileptic drugs are generally needed to achieve therapeutic effects. Lipidnanoparticles (LNs) are promising systems aimed to surpass this limitation. LNs of miristilmiristate containg phenobarbital were designed and optimized in terms of sizeand charge by a QbD approach. The formulation with the highest desirability wasthen prepared by ultrasonication, and characterized by means of entrapmentefficiency (EE), particle size, polydispersity and z-potential. Thermalproperties were analysed by DSC and TGA, and morphology and crystal propertiesby AFM and XRD. Drug localization was evaluated using FTIR. In vitro release and in vivo anticonvulsant activity in ananimal model of acute seizures were studied. The optimized LNs showedspherical particles with particle size ca. 178 nm and 98.2% of EE. It was thermicallystable and the drug was homogeneously distributed within the lipid matrix. Sustainedrelease kinetic of the drug was observed invitro, and the in vivo assayconfirmed the anticonvulsant activity of the LNs. These are very promisingresults which positions these systems as a possible alternative to traditional epilepsytreatments.