Caroline Hermann Nodari1, Natália Dalanhol De Quadros1, Raquel Chiarentin1, Francini Pereira Da Silva2, Fernando Dal Pont Morisso3, Mariele Feiffer Charão1, Juliane Deise Fleck1,2, Cristiane Bastos De Mattos1,3, Andresa Heemann Betti1, Simone Gasparin Verza4,5. 1. Bioanalysis Laboratory, Institute of Health Sciences, Feevale University, 2755 Rodovia ERS 239, Novo Hamburgo, RS, CEP 93352-000, Brazil. 2. Molecular Microbiology Laboratory, Institute of Health Sciences, Feevale University, Novo Hamburgo, RS, Brazil. 3. Advanced Materials Laboratory, Institute of Health Sciences, Feevale University, Novo Hamburgo, RS, Brazil. 4. Bioanalysis Laboratory, Institute of Health Sciences, Feevale University, 2755 Rodovia ERS 239, Novo Hamburgo, RS, CEP 93352-000, Brazil. simonev@feevale.br. 5. Molecular Microbiology Laboratory, Institute of Health Sciences, Feevale University, Novo Hamburgo, RS, Brazil. simonev@feevale.br.
Abstract
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).
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).
Authors: Michael E Thase; Atul R Mahableshwarkar; Marianne Dragheim; Henrik Loft; Eduard Vieta Journal: Eur Neuropsychopharmacol Date: 2016-03-25 Impact factor: 4.600
Authors: Michael E Thase; Natalya Danchenko; Melanie Brignone; Ioana Florea; Francoise Diamand; Paula L Jacobsen; Eduard Vieta Journal: Eur Neuropsychopharmacol Date: 2017-06-27 Impact factor: 4.600
Authors: Tarek M Ibrahim; Margrit M Ayoub; Hany M El-Bassossy; Hanan M El-Nahas; Eman Gomaa Journal: Pharmaceutics Date: 2022-09-05 Impact factor: 6.525