Carbamazepine-loaded solid lipid nanoparticles and nanostructured lipid carriers: physicochemical characterization and in vitro / in vivo evaluation

SCIOLI MONTOTO, S.; SBARAGLINI, M.L.; TALEVI, A.; COUYOUPETROU, M.; DI IANNI, M.; PESCE, G.O.; ALVAREZ, V.A.; BRUNO-BLANCH, L.E.; CASTRO, G.R.; RUIZ, M.E.; ISLAN, G.A.

COLLOIDS AND SURFACES B-BIOINTERFACES

ELSEVIER SCIENCE BV

Lugar: Amsterdam; Año: 2018 vol. 167 p. 73 - 81

0927-7765

Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) represent promising alternativesfor drug delivery to the central nervous system. In the present work, four different nanoformulationsof the antiepileptic drug Carbamazepine (CBZ) were designed and prepared by the homogeniza-tion/ultrasonicationmethod, withencapsulationefficiencies ranging from82.8 to 93.8%. The formulationsremained stable at 4 ◦C for at least 3 months. Physicochemical and microscopic characterization wereperformed by photon correlation spectroscopy (PCS), transmission electron microscopy (TEM), atomicforce microscopy (AFM); thermal properties by differential scanning calorimetry (DSC), thermogravime-try (TGA) and X-ray diffraction analysis (XRD). The results indicated the presence of spherical shapenanoparticles with a mean particle diameter around 160 nm in a narrow size distribution; the entrappedCBZ displayed an amorphous state. The in vitro release profile of CBZ fitted into a Baker-Lonsdale modelfor spherical matrices and almost the 100% of the encapsulated drug was released in a controlled mannerduring the first 24 h. The apparent permeability of CBZ-loaded nanoparticles through a cell monolayermodel was similar to that of the free drug. In vivo experiments in a mice model of seizure suggestedprotection by CBZ-NLC against seizures for at least 2 h after intraperitoneal administration. The devel-oped CBZ-loaded lipid nanocarriers displayed optimal characteristics of size, shape and drug releaseand possibly represent a promising tool to improve the treatment of refractory epilepsy linked to effluxtransporters upregulation.