Carreadores lipídicos nanoestruturados carregados com canabidiol para administração intranasal: desenvolvimento, caracterização e estudos in vivo

Abstract

Cannabidiol (CBD) has been studied for the treatment of several pathologies, including neuropathic pain. Oral administration of CBD has very low bioavailability, due to its low solubility and extensive hepatic metabolism. Therefore, the present study aimed to develop nanostructured lipid carriers os systems for intranasal administration of CBD. Nanostructured lipid carriers loaded with cannabidiol (CBD-NLC) were prepared by the hot microemulsification technique and had a particle size of less than 200 nm, polydispersity index around 0.3 and high drug encapsulation efficiency. The zeta potential above 40 mV, provided NLC with mucoadhesive properties. Analysis by atomic force microscopy showed spherical particles, nanometric and smooth surface. And studies of differential exploratory calorimetry, X-ray diffraction and infrared spectroscopy suggested the incorporation of the drug in molecular dispersion in the lipid matrix. Subsequently, the addition of 20% of Poloxamer® 407 and Pluronic® F68 polymers in the 17:3 ratio made it possible to gel the dispersion of the NLC at the temperature of the nasal cavity. Rheological studies, texture and mucoadhesion analysis have shown that the formulation showed a pseudoplastic and thixotropic behavior, which is a feature that facilitates administration, in addition to being cohesive and mucoadhesive at the gelation temperature, demonstrating the ability of the formulation to resist mucociliary clearance. The release of CBD from the formulations demonstrated a sustained profile. However, the release from the NLC-gel was very low, probably due to the viscosity and hydrophilicity of the polymeric matrix of the gel. In vivo studies have shown that the nasal administration of CBD-NLC showed greater antinociceptive efficacy in mice with chemotherapy-induced neuropathic pain, when compared to the administration of CBD solution, both through the nasal and the oral route, suggesting that the CBD-NLC have great potential for nasal CBD administration.