Buspirone loaded solid lipid nanoparticles for amplification of nose to brain efficacy: Formulation development, optimization by Box-Behnken design, in-vitro characterization and in-vivo biological evaluation

Abstract

The strategies to avoid blood brain barrier are been explored to improve brain targeting therapeutics in order to ensure potential prospects of nose to brain delivery. In this research work, Buspirone (BUS) loaded solid lipid nanoparticles (SLNs) for nose to brain delivery were prepared by solvent free technique and optimized by three factors and three levels Box- Behnken design. The three independent variables viz, drug (BUS) to lipid (Compritol® 888 ATO) ratio (labeled A), surfactant concentration (tween 80+ poloxamer, 2:1- labeled B) and sonication time (labeled C) were selected in range of 1:3–1:5, 1–2% and 5–15 min respectively. Their influences on particle size (nm, labeled Y1), Polydispersity index (PDI, labeled Y2) and % entrapment efficiency (labeled Y3) were observed. Optimized batch (B-OP3) showed spherical morphology possessing the value of particle size, PDI, zeta potential, entrapment efficiency, and in-vitro drug release as 218.60 ± 9.18 nm, 0.305 ± 0.012, −26.47 ± 2.36 mV, 70.13 ± 4.21% and 93.36 ± 8.63% respectively. BUS-SLNs displayed superior ex-vivo permeation profiles as compared to BUS-Sol. X-ray diffraction and differential scanning calorimetry spectra do not display the characteristic peak of BUS, thus recommending the entrapment of drug in lipid core. AUC 0-∞ in the brain for BUS-SLNs i.n was found to be 2.18 times more than BUS-Sol i.n and 2.66 times more than BUS-SLNs i.v., thus supporting improved targeting efficiency of developed SLNs. The value of drug targeting efficiency (DTE) percentage to brain (882.59%) and nose to brain direct transport (DTP) percentage (88.67%) for BUS-SLNs i.n was higher as compared to BUS-Sol i.n (DTE = 238.63%, DTP = 58.09%). Furthermore, confocal laser scanning microscopy study confirmed that brain targeting of BUS-SLNs was better than BUS-Sol when administered intranasally. Finally, results revealed that SLNs establish itself as a potential drug delivery system for brain delivery of BUS via intranasal route.