Bougainvillea glabra Choisy bracts extract in free and liposomal forms reduce hyperplasia induced by let-60gain-of-function in Caenorhabditis elegans.

In this study, we evaluated the toxicological and antiproliferative effects of B. glabra Choisy bract extract (BGCE) in its free and loaded into liposomes forms administered to C. elegans mutants with let-60 gain-of-function (gf). Our results demonstrated that the concentration up to 75 µg CAE/mL of BGCE was safe for the worms. Notably, we developed BGCE-loaded liposomes to extend the pharmacological window up to 100 µg CAE/mL without toxicity. In addition, the extract and liposomes reduced the number and area of the multivulva formed in let-60 gf mutants. There was also an increase in the apoptotic signaling in the germline cells and increased longevity mediated through DAF-16 nuclear translocation with GST-4 activation in the treated animals. Our findings demonstrated that the BGCE-loaded liposomes possess antitumoral effects due to the activation of the apoptotic signaling and DAF-16 nuclear translocation.

In silico evidences of Mpro inhibition by a series of organochalcogen-AZT derivatives and their safety in Caenorhabditis elegans.

BACKGROUND: The new coronavirus (SARS-CoV-2) pandemic emerged in 2019 causing millions of deaths. Vaccines were quickly developed and made available in 2021. Despite the availability of vaccines, some subjects refuse to take the immunizing or present comorbities, therefore developing serious cases of COVID-19, which makes necessary the development of antiviral drugs. Previous studies have demonstrated that ebselen, a selenium-containing molecule, can inhibit SARS-CoV-2 Mpro. In addition, selenium is a trace element that has antiviral and anti-inflammatory properties. Zidovudine (AZT) has been widely used against HIV infections and its action against SARS-CoV-2 may be altered by the structural modification with organochalcogen moieties, but this hypothesis still needs to be tested. METHODS: In the present work we evaluated the Mpro inhibition capacity (in silico), the safety and antioxidant effect of six organochalcogen AZT-derivatives using the free-living nematode Caenorhabditis elegans, through acute (30 min) and chronic (48) exposure protocols. RESULTS: We observed that the molecules were safe at a concentration range of 1-500 µM and did not alter any toxicological endpoint evaluated. Furthermore, the molecules are capable to decrease the ROS formation stimulated by hydrogen peroxide, to modulate the expression of important antioxidant enzymes such superoxide-dismutase-3 and glutathione S-transferese-4 and to stimulate the translocation of the DAF-16 to the cell nucleus. In addition, the molecules did not deplete thiol groups, which reinforces their safety and contribution to oxidative stress resistance. CONCLUSIONS: We have found that compounds S116l (a Tellurium AZT-derivative) and S116h (a Selenium-AZT derivative) presented more promising effects both in silico and in vivo, being strong candidates for further in vivo studies.

Acaricides containing zein nanoparticles: A tool for a lower impact control of the cattle tick Rhipicephalus microplus.

Nanoformulations containing zein nanoparticles (ZN) can promote the stability and protection of molecules with acaricidal activity. The present study sought to develop nanoformulations with ZN associated with cypermethrin (CYPE) + chlorpyrifos (CHLO) + a plant compound (citral, menthol or limonene), characterize them, and verify their efficacy against Rhipicephalus microplus ticks. Additionally, we aimed to assess its safety in nontarget nematodes found in soil at a site subjected to contamination by acaricides. The nanoformulations were characterized by dynamic light scattering and nanoparticle tracking analysis. Nanoformulations 1 (ZN+CYPE+CHLO+citral), 2 (ZN+CYPE+CHLO+menthol), and 3 (ZN+CYPE+CHLO+limonene) were measured for diameter, polydispersion, zeta potential, concentration, and encapsulation efficiency. Nanoformulations 1, 2, and 3 were evaluated in a range from 0.004 to 0.466 mg/mL on R. microplus larvae and caused mortality > 80% at concentrations above 0.029 mg/mL. The commercial acaricide Colosso® (CYPE 15 g + CHLO 25 g + citronellal 1 g) was evaluated also from 0.004 to 0.512 mg/mL and resulted in 71.9% larval mortality at 0.064 mg/mL. Formulations 1, 2, and 3 at 0.466 mg/mL showed acaricidal efficacy of 50.2%, 40.5%, and 60.1% on engorged females, respectively, while Colosso® at 0.512 mg/mL obtained only 39.4%. The nanoformulations exhibited long residual period of activity and lower toxicity to nontarget nematodes. ZN was able to protect the active compounds against degradation during the storage period. Thus, ZN can be an alternative for the development of new acaricidal formulations using lower concentrations of active compounds.

Co-encapsulation of acyclovir and curcumin into microparticles improves the physicochemical characteristics and potentiates in vitro antiviral action: Influence of the polymeric composition.

The present study developed and characterized microparticles formulations containing acyclovir and curcumin co-encapsulated in order to overcome the biopharmaceutical limitations and increase the antiviral effect of both drugs. The microparticles were prepared by a spray drying methodology following the ratio 1:3 (drug:polymer), which were made by hydroxypropylmethylcellulose (HPMC) and/or Eudragit® RS100 (EUD). The MP-1 formulation was composed of HPMC and EUD (1:1), MP-2 formulation was composed only of HPMC and MP-3 formulation was composed only of EUD. All formulations showed yielding around 50% and acceptable powder flowability. Drug content determination around 82.1-96.8% and 81.8-87% for acyclovir and curcumin, respectively. The microparticles had spherical shape, size within 11.5-15.3 µm, unimodal distribution and no chemical interactions among the components of the formulations. Of particular importance, the polymeric composition considerably influenced on the release profile of the drugs. The in vitro release experiment demonstrated that the microencapsulation provided a sustained release of acyclovir as well as increased the solubility of curcumin. Besides, mathematical modeling indicated that the experimental fit biexponential equation. Importantly, drugs microencapsulation promoted superior antiviral effect against BoVH-1 virus in comparison to their free form, which could be attributed to the improvement in the aforementioned physicochemical parameters. Therefore, these formulations could be promising technological drug carriers for acyclovir and curcumin, which highlight the great offering a potential alternative treatment for viral herpes.