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.

Antiproliferative activity and toxicity evaluation of 1,2,3-triazole and 4-methyl coumarin hybrids in the MCF7 breast cancer cell line.

Four coumarin-triazole hybrids were selected from our in house library and screened for cytotoxic activity on A549 (lung cancer), HepG2 (liver cancer), J774A1 (mouse sarcoma macrophage), MCF7 (breast cancer), OVACAR (ovarian cancer), RAW (murine leukaemia macrophage), and SiHa (uterus carcinoma) and their in vitro toxicity was assessed on 3T3 (healthy fibroblasts) cell lines. SwissADME pharmacokinetic prediction was performed. Effects on ROS production, mitochondrial membrane potential, apoptosis/necrosis and DNA damage were evaluated. All of the hybrids have good pharmacokinetic predictions. Each of them showed cytotoxic activity against the MCF7 breast cancer cell line, with IC50 between 2.66 and 10.08 µM, lower than cisplatin (45.33 µM) for the same test. One can observe an order of reactivity from the most potent: LaSOM 186 > LaSOM 190 > LaSOM 185 > LaSOM 180, with a better selectivity index than the reference drug cisplatin and the precursor hymecromone, and caused cell death by apoptosis induction. Two compounds showed antioxidant activity in vitro and three disrupted the mitochondrial membrane potential. None of the hybrids caused genotoxic damage to healthy 3T3 cells. All hybrids showed potential for further optimization, mechanism elucidation, in vivo activity and toxicity tests.