Development and pharmacological evaluation of liposomes and nanocapsules containing paroxetine hydrochloride.

Depression is one of the most common psychiatric disorders. Nanotechnology has emerged to optimize the pharmacological response. Therefore, the aim of this work was to develop and characterize liposomes and nanocapsules containing paroxetine hydrochloride and evaluate their antidepressant-like effect using the open field and tail suspension tests in mice. Liposomes and nanocapsules were prepared using the reverse-phase evaporation and nanoprecipitation methods, respectively. The particle size of the formulation ranged from 121.81 to 310.73 nm, the polydispersity index from 0.096 to 0.303, the zeta potential from -11.94 to -34.50 mV, the pH from 5.31 to 7.38, the drug content from 80.82 to 94.36 %, and the association efficiency was 98 %. Paroxetine hydrochloride showed slower release when associated with liposomes (43.82 %) compared to nanocapsules (95.59 %) after 10 h. In Vero cells, in vitro toxicity showed a concentration-dependent effect for paroxetine hydrochloride nanostructures. Both nanostructures decreased the immobility time in the TST at 2.5 mg/kg without affecting the number of crossings in the open field test, suggesting the antidepressant-like effect of paroxetine. In addition, the nanocapsules decreased the number of groomings, reinforcing the anxiolytic effect of this drug. These results suggest that the nanostructures were effective in preserving the antidepressant-like effect of paroxetine hydrochloride even at low doses.

Vortioxetine liposomes as a novel alternative to improve drug stability under stress conditions: toxicity studies and evaluation of antidepressant-like effect.

BACKGROUND: Vortioxetine hydrobromide (VXT), a new therapeutic option in the treatment of major depressive disorder, is a poorly soluble drug, and instability under stress conditions has been reported. The aim of the present study was to prepare VXT liposomes (VXT-Ls) with an antidepressant-like effect, to improve drug stability and reduce toxicity of the free drug. METHODS: Liposomes were prepared using the thin lipid film hydration method and properly characterized. Forced degradation studies were conducted in photolytic and oxidative conditions. The cytotoxicity was evaluated in VERO cells through MTT assay and in vivo toxicity was assessed in mice. The antidepressant-like effect in mice was confirmed using the open-field test paradigm and tail suspension test. RESULTS: The optimized VXT-Ls have multilamellar vesicles with an average size of 176.74 nm ± 2.43. The liposomal formulation increased the stability of VXT. VERO cell viability was maintained at around 40% when the VXT-Ls were tested at higher concentrations and no signs of acute toxicity were observed in mice. The antidepressant-like effect was effective, for VXT-Ls, at doses ranging from 2.5 mg/kg to 10 mg/kg, measured by the tail suspension test in mice. The non-liposomal formulation was effective at a dose of 10 mg/kg. The open field test was performed and any unspecific changes in locomotor activity were revealed. CONCLUSIONS: Liposomes seem to be a promising alternative for an oral VXT formulation at lower doses (2.5 mg/kg).