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.

Caenorhabditis elegans as a suitable model to evaluate the toxicity of water from Rolante River, southern Brazil.

Urbanization and agricultural activities increased environmental contaminants. Integrated analysis of water parameters and bioassays represents an essential approach to evaluating aquatic resource quality. This study aimed to assess water quality by microbiological and physicochemical parameters as well as the toxicological effects of water samples on the Ames test and Caenorhabditis elegans model. Samples were collected during (collection 1) and after (collection 2) pesticide application in the upper (S1), middle (S2), and lower (S3) sections of the Rolante River, southern Brazil. Metals were determined by GFAAS and pesticides by UPLC-MS/MS. Bioassays using the Ames test and the nematode C. elegans were performed. Levels of microbiological parameters, as well as Mn and Cu were higher than the maximum allowed limits established by legislation in collection 2 compared to collection 1. The presence of pesticide was observed in both collections; higher levels were found in collection 1. No mutagenic effect was detected. Significant inhibition of body length of C. elegans was found in collection 1 at S2 (P < 0.001) and S3 (P < 0.001) and in collection 2 at S2 (P = 0.004). Comparing the same sampling site between collections, a significant difference was found between the site of collection (F(3,6)=8.75, P = 0.01) and the time of collection (F(1,2)=28.61, P = 0.03), for the S2 and S3 samples. C. elegans model was useful for assessing surface water quality/toxicity. Results suggest that an integrated analysis for the surface water status could be beneficial for future approaches.

Pervasive transmission of E484K and emergence of VUI-NP13L with evidence of SARS-CoV-2 co-infection events by two different lineages in Rio Grande do Sul, Brazil.

Emergence of novel SARS-CoV-2 lineages are under the spotlight of the media, scientific community and governments. Recent reports of novel variants in the United Kingdom, South Africa and Brazil (B.1.1.28-E484K) have raised intense interest because of a possible higher transmission rate or resistance to the novel vaccines. Nevertheless, the spread of B.1.1.28 (E484K) and other variants in Brazil is still unknown. In this work, we investigated the population structure and genomic complexity of SARS-CoV-2 in Rio Grande do Sul, the southernmost state in Brazil. Most samples sequenced belonged to the B.1.1.28 (E484K) lineage, demonstrating its widespread dispersion. We were the first to identify two independent events of co-infection caused by the occurrence of B.1.1.28 (E484K) with either B.1.1.248 or B.1.91 lineages. Also, clustering analysis revealed the occurrence of a novel cluster of samples circulating in the state (named VUI-NP13L) characterized by 12 lineage-defining mutations. In light of the evidence for E484K dispersion, co-infection and emergence of VUI-NP13 L in Rio Grande do Sul, we reaffirm the importance of establishing strict and effective social distancing measures to counter the spread of potentially more hazardous SARS-CoV-2 strains.