Shahiq Uz Zaman

The potential of levosulpiride-loaded nanostructured lipid carriers (LSP-NLCs) for enhanced antidepressant and anxiolytic effects was evaluated in the current study. A forced swim test (FST) and tail suspension test (TST) were carried out to determine the antidepressant effect whereas anxiolytic activity was investigated using light–dark box and open field tests. Behavioral changes were evaluated in lipopolysaccharide-induced depressed animals. The access of LSP to the brain to produce therapeutic effects was estimated qualitatively by using fluorescently labeled LSP-NLCs. The distribution of LSP-NLCs was analyzed using ex vivo imaging of major organs after oral and intraperitoneal administration. Acute toxicity studies were carried out to assess the safety of LSP-NLCs in vivo. An improved antidepressant effect of LSP-NLCs on LPS-induced depression showed an increase in swimming time (237 ± 51 s) and struggling time (226 ± 15 s) with a reduction in floating (123 ± 51 s) and immobility time (134 ± 15 s) in FST and TST. The anxiolytic activity in the light–dark box and open field tests exhibited superiority over LSP dispersion. Near-infrared images of fluorescently labeled LSP-NLCs demonstrated the presence of coumarin dye in the brain after 1 h of administration. An acute toxicity study revealed no significant changes in organ-to-body weight ratio, serum biochemistry or tissue histology of major organs. It can be concluded that nanostructured lipid carriers can efficiently deliver LSP to the brain for improved therapeutic efficacy.

The present study is aimed to develop and optimize levosulpiride-loaded nanostructured lipid carriers (LSP-NLCs) for improving oral bioavailability and prokinetic activity of LSP. LSP-NLCs were optimized with D-optimal mixture design using solid lipid, liquid lipid and surfactant concentrations as independent variables. The prepared LSP-NLCs were evaluated for physicochemical properties and solid-state characterization. The in vivo oral pharmacokinetics and prokinetic activity of LSP-NLCs were evaluated in rats. LSP-NLCs formulation was optimized at Precirol^® ATO 5/Labrasol (80.55/19.45%, w/w) and Tween 80/Span 80 concentration of 5% (w/w) as a surfactant mixture. LSP-NLCs showed a spherical shape with a particle size of 152 nm, a polydispersity index of 0.230 and an entrapment efficiency of 88%. The DSC and PXRD analysis revealed conversion of crystalline LSP to amorphous state after loading into the lipid matrix. LSP-NLCs displayed a 3.42- and 4.38-flods increase in AUC and C_max after oral administration compared to LSP dispersion. In addition, LSP-NLCs showed enhanced gastric emptying (61.4%), intestinal transit (63.0%), and fecal count (68.8) compared to LSP dispersion (39.7%, 38.0% and 51.0, respectively). Taken together, these results show improved oral bioavailability and prokinetic activity of LSP-NLCs and presents a promising strategy to improve therapeutic activity of LSP for efficient treatment of gastric diseases.