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

SCIOLI MONTOTO, S; SBARAGLINI, ML; CISNEROS, JOSE SEBASTIAN; CHAIN, CY; VELA, ME; TALEVI, A; ALVAREZ, VA; CASTRO, GR; RUIZ, ME

Córdoba

Congreso; 6ta Reunión Internacional de Ciencias Farmacéuticas (RICiFa 2020+1); 2021

Epilepsy is one of the most common neurological disorders, affecting around 50 million people worldwide. Due to the restrictions imposed by the blood brain barrier, high doses of antiepileptic drugs (AEDs) are generally needed to achieve therapeutic effects. Lipid nanoparticles (LNs) are promising systems aimed to improve or surpass this limitation. LNs containg the AED phenobarbital were designed and optimized by Quality by Design approach. The optimized formulation was then prepared by homegenization by ultrasonication. and characterized by means of its entrapment efficiency, paricle size, polydispersity index and z-potential. Thermal properties were analysed by DSC and TGA, and morphology and crystal properties by AFM and XRD. Drug localization was evaluated using FTIR. In vitro release kinetic, and in vivo anticonvulsant activity in an animal model of acute seizures were studied.The optimized formulation showed spherical particles with particle size ca. 178 nm and 98.2% of entrapment efficiency. It was thermically stable and the drug was homogeneously distributed within the lipid matrix. Sustained release kinetic of the drug was observed in vitro, and the in vivo assay confirmed the anticonvulsant properties of the formulation. These are very promising results which positions these systems as a possible alternative to traditional epilepsy treatments.