Fabrication data of two light-responsive systems to release an antileishmanial drug activated by infrared photothermal heating.

The data provided in this study are related to the fabrication of two light-responsive systems based on reduced graphene oxide (rGO) functionalized with the polymers Pluronic P123 (P123), rGO-P123, and polyethyleneimine (PEI), rGO-PEI, and loaded with amphotericin B (AmB), an antileishmanial drug. Here are described the experimental design to obtain the systems and characterization methods, such as Attenuated Total Reflectance-Fourier Transform Infrared Spectroscopy (ATR-FTIR), Raman Spectroscopy, Powder X-Ray Diffraction, Transmission Electron Microscopy, Scanning Electron Microscopy and Thermogravimetric Analyses. Also, AmB spectroscopy studies are described. The materials rGO-P123 and rGO-PEI were loaded with AmB and the optimization of AmB and polymer fragments structures revealed several possible hydrogen bonds formed between the materials and the drug. The drug release was analyzed with and without Near-Infrared (NIR) light. In the studies conducted under NIR light irradiation for 10 min, an infrared lamp was disposed at 64 cm from the samples and an optical fiber thermometer was employed to measure the temperature variation. Cytotoxicity studies and antiproliferative assays against Leishmania amazonensis promastigotes were evaluated. The complete work data entitled Amphotericin-B-Loaded Polymer-Functionalized Reduced Graphene Oxides for Leishmania amazonensis Chemo-Photothermal Therapy have been published to Colloids and Surfaces B: Bionterfaces (https://doi.org/10.1016/j.colsurfb.2021.112169) [1].

Amphotericin-B-loaded polymer-functionalized reduced graphene oxides for Leishmania amazonensis chemo-photothermal therapy.

Two platforms based on reduced graphene oxide (rGO) functionalized with Pluronic® P123 (rGO-P123) and polyethyleneimine - PEI (rGO-PEI) polymers and loaded with amphotericin B (AmB) were fabricated and tested against Leishmania amazonensis, which can cause cutaneous and diffuse cutaneous leishmaniasis. The materials rGO-P123 and rGO-PEI were efficiently loaded with AmB - a polyene antibiotic - which resulted in rGO-P123-AmB (0.078 mg per mg of material) and rGO-PEI-AmB (0.086 mg per mg of material). Under near-infrared (NIR) light irradiation, the amount of AmB released from rGO-PEI-AmB at pH 5.0 and 7.4 doubled in comparison to AmB released in the absence of NIR light under identical conditions. It was accompanied by a photothermal effect. Otherwise, rGO-P123-AmB did not show a significant change in AmB released in the presence and absence of NIR light. Cytotoxicity studies in mammalian host macrophages revealed that rGO-PEI and rGO-PEI-AmB were nontoxic to the host cells, whereas rGO-123 and rGO-P123-AmB were very toxic, particularly the latter. Therefore, only rGO-PEI and rGO-PEI-AmB were tested against L. amazonensis promastigotes in the presence and absence of NIR light. In vitro antiproliferative effects revealed that rGO-PEI-AmB showed a more pronounced activity against the parasite than rGO-PEI, which was improved under NIR light irradiation. Scanning-transmission electron microscopy of L. amazonensis promastigotes after incubation with rGO-PEI or rGO-PEI-AmB suggested autophagic and necrotic cell death. Thus, the facile synthesis, high AmB loading capacity and good photothermal effect make the rGO-PEI-AmB platform a promising candidate for the topical treatment of cutaneous leishmaniasis.

A Carbocationic Triarylmethane-Based Porous Covalent Organic Network.

A thermally stable carbocationic covalent organic network (CON), named RIO-70 was prepared from pararosaniline hydrochloride, an inexpensive dye, and triformylphloroglucinol in solvothermal conditions. This nanoporous organic material has shown a specific surface area of 990 m2 g-1 and pore size of 10.3 Å. The material has CO2 uptake of 2.14 mmol g-1 (0.5 bar), 2.7 mmol g-1 (1 bar), and 6.8 mmol g-1 (20 bar), the latter corresponding to 3 CO2 molecules adsorbed per pore per sheet. It is shown to be a semiconductor, with electrical conductivity (σ) of 3.17×10-7  S cm-1 , which increases to 5.26×10-4  S cm-1 upon exposure to I2 vapor. DFT calculations using periodic conditions support the findings.

A reversible, switchable pH-driven quaternary ammonium pillar[5]arene nanogate for mesoporous silica nanoparticles.

Here we describe the assembly and pH-driven operation of two nanocarriers based on non-functionalized (MCM-41) and carboxylate-functionalized (MCM-41-COOH) containers loaded with the anticancer drug doxorubicin (DOX) and capped by quaternary ammonium pillar[5]arene (P[5]A) nanogates. MCM-41 and MCM-41-COOH containers were synthesized and transmission and scanning electron microscopies showed nanoparticles with spherical morphology and dimensions of 85 ± 13 nm. The nanochannels of MCM-41 loaded with DOX were gated through the electrostatic interactions between P[5]A and the silanolate groups formed at the silica-water interface, yielding the MCM-41-DOX-P[5]A nanocarrier. The second nanocarrier was gated through the electrostatic interactions between the carboxylate groups mounted on the surface of MCM-41 and P[5]A, resulting in the MCM-41-COO-DOX-P[5]A nanocarrier. The DOX release profiles from both nanocarriers were investigated by UV-vis spectroscopy at different pH values (2.0, 5.5 and 7.4) and also in the presence of ions, such as citrate3- (19 mmol L-1) and Zn2+ (1.2 and 50 mmol L-1) at 37 °C. MCM-41-COO-DOX-P[5]A can be turned on and off eight times through the formation and breaking of electrostatic interactions. In vitro studies show that MCM-41-COO-DOX-P[5]A can penetrate and release DOX in the nucleus of human breast adenocarcinoma MCF-7 cancer cells leading to a pronounced cytotoxic effect. Therefore, the fabricated nanocarrier based on a water-soluble cationic pillar[5]arene nanogate, which is reversibly opened and closed by electrostatic interactions, can be considered as a promising drug transport and delivery technique for future cancer therapy.

Multifunctional System Polyaniline-Decorated ZIF-8 Nanoparticles as a New Chemo-Photothermal Platform for Cancer Therapy.

Polyaniline-decorated ZIF-8 nanoparticles (nPANI@nZIF-8) were easily synthesized and employed as a multifunctional system for the delivery of the antitumor drug 5-fluorouracil (5-FU). Because of the storage ability of the network ZIF-8, 68% of the total amount of the 5-FU drug was released at pH 5.2. The system exhibits absorption in the near-infrared (NIR) region and can be used in the photothermal therapy owing to the presence of nPANI, which has a strong NIR uptake. This absorption causes local hyperthermia by aiding in the diffusion of the drug molecules contained by the polymer into nPANI@nZIF-8/5-FU achieving a greater release of the 5-FU drug, about 80% activated by an NIR laser (λ = 980 nm). This hyperthermia reached about 70 °C (200 µL, 1 mg mL-1 nPANI@nZIF-8), which was directly proportional to the concentration of the material. Therefore, our work can aid in the construction of new chemo-photothermal platforms that may be employed in cancer therapy.

Avaliação dos efeitos miorelaxante, antiespasmódico e antinociceptivo do extrato aquoso da Phoradendron piperoides (Kunt.) Trel. (Viscaceae) / Investigation on miorelaxant, antispasmodic and analgesic effects of the aqueous extract of Phoradendron piperoides

Foram investigados os efeitos miorelaxante, antiespasmódico e antinociceptivo do extrato aquoso liofilizado das folhas da Phoradendron piperoides. A toxicidade aguda também foi avaliada. No íleo isolado de cobaio, o extrato aquoso da P. piperoides (0,05 - 2,0 mg/mL) produziu relaxamento de forma concentração-dependente (IC50 = 0,114 mg/mL) e, na concentração de 1,5 mg/mL, reduziu a amplitude das contrações induzidas por carbacol (2 μM), histamina (2 μM) e BaCl2 (0,03 M) em 46,6; 38,6 e 55,3 por cento (p < 0,001), respectivamente. Em camundongos, o extrato aquoso liofilizado (100-400 mg/kg) não reduziu de forma significativa as contorções abdominais induzidas por ácido acético, não modificou o tempo de reação dos animais no teste da formalina e não aumentou o tempo de latência ao calor no teste da placa quente. No ensaio de toxicidade aguda utilizado, não foi detectada a morte de nenhum animal após tratamento com doses de até 5 g/kg (p.o.) do extrato. Em conclusão, os resultados obtidos indicam que o extrato aquoso da P. piperoides apresenta efeito antiespasmódico e baixa toxicidade aguda. O extrato, no entanto, não possui efeito antinociceptivo.

The present work evaluated the antinociceptive, miorelaxant and antispasmodic effects as well as the acute toxicity of the aqueous extract from leaves of Phoradendron piperoides. In guinea pig ileum, the plant extract (0.05 - 2.0 mg/kg) decreased the preparations basal tone in a dose-dependent manner (IC50 = 0.114 mg/mL) and it (1.5 mg/mL) reduced (p < 0.001) the contractions induced by carbachol (2 μM), histamine (2 μM) and BaCl2 (0.03M). The extract, at oral doses of 100, 200, and 400 mg/kg, did not manifest a significant antinociceptive effect in the writhing, formalin and hot-plate tests. Moreover, no animal deaths were observed in doses up to 5 g/kg. In conclusion, the aqueous extract of Phoradendron piperoides showed no antinociceptive effect and no acute toxicity in mice. Indeed, it revealed miorelaxant and antispasmodic activities that are probably miogenic and not specific for neurotransmitters.

Antinociceptive activity of Maytenus rigida stem bark.

Ethanol extract of Maytenus rigida stem bark and its fractions were assessed for antinociceptive activity in tail-flick test in rats. The activity was located in the chloroform, ethyl acetate and aq.methanol fractions. Phytochemical screening revealed that catechin was the only common class of compounds present on the ethanol extract as well as on the active fractions. 4'-Methylepigallocatechin, isolated from the ethyl acetate and aq.methanol fractions, showed antinociceptive effect in the tail-flick test (75 mg/kg; p.o.), which was reversed by the opiate antagonist naloxone (3 mg/kg; i.p.).

Antinociceptive effect and acute toxicity of the Hyptis suaveolens leaves aqueous extract on mice.

The aqueous extract of Hyptis suaveolens leaves was studied for their antinociceptive property in chemical and thermal models of nociception in mice. Oral administration of the aqueous extract (100, 200, and 400 mg/kg) dose-dependently reduced the number of writhings induced by acetic acid, decreased the licking activity of the early phase in formalin test and increased the reaction time in hot-plate test. The antinociceptive effect was significantly antagonized by naloxone (3 mg/kg; i.p.). Preliminary acute toxicity study showed that no animal death with doses up to 5 g/kg (p.o.).

Antinociceptive effect and acute toxicity of the essential oil of Hyptis fruticosa in mice.

The essential oil of the Hyptis fruticosa leaves was analyzed by GC/MS and evaluated for antinociceptive property as well as acute toxicity in mice. The essential oil, at doses of 100, 200, and 400 mg/kg (s.c.), produced significant inhibition of acetic acid-induced writhing, but did not manifest a significant effect in hot-plate test. There was no acute toxicity at doses up to 5 g/kg. Bicyclogermacrene, 1,8-cineole, alpha-pinene, and beta-caryophyllene were the major compounds detected in the essential oil.

Avaliação do efeito antinociceptivo e da toxicidade aguda do extrato aquoso da Hyptis fruticosa Salmz. ex Benth / Evaluation of the analgesic effect and acute toxicity of the aqueous extract of Hyptis fruticosa (Salmz. ex Benth.)

Este trabalho descreve o efeito antinociceptivo e a toxicidade aguda do extrato aquoso das folhas da Hyptis fruticosa Salmz. ex Benth. (Lamiaceae). O extrato aquoso liofilizado, administrado por via oral, reduziu as contorções abdominais induzidas por ácido acético (200, 400 e 500 mg/kg) e o tempo de reação dos animais na primeira fase do teste da formalina (100 mg/kg e 400 mg/kg). No teste da placa quente, o extrato aquoso aumentou o tempo de latência ao calor (100 e 200 mg/kg) tendo este efeito sido revertido pelo antagonista opióide naloxona (5 mg/kg; i.p.). No ensaio de toxicidade aguda, não foi detectada a morte de nenhum animal após tratamento com doses de até 5 g/kg (v.o.) do extrato. Em conclusão, os resultados obtidos indicam que o extrato aquoso da Hyptis fruticosa apresenta efeito antinociceptivo em camundongos e não apresenta toxicidade aguda nas doses testadas.

The antinociceptive effect and the acute toxicity of Hyptis fruticosa leaves were evaluated through the administration of its aqueous extract in mice. The extract, administered orally (200, 400, and 500 mg/kg), reduced the nociceptive response in the writhing test as well as in the early phase of the formalin test (100 and 400 mg/kg) and it increased the latency time in the hot plate test (100 and 200 mg/kg). The antinociceptive effect was reversed by naloxone (5 mg/kg, i.p.). Moreover, no animal deaths were observed in doses up to 5 g/kg. In conclusion, the aqueous extract of Hyptis fruticosa showed no acute toxicity at the evaluated doses and revealed antinociceptive effect in mice. Such effects are possibly associated with the opioid system activation.

A prevalência de fatores de risco para baixa adesão na terapia com enfuvirtida, nos usuários soropositivos para o HIV em tratamento nos centros de referência em Porto Alegre - RS / The prevalence of risk factors for decreasing adhesion in the therapy with enfuvirtida in HIV infected users in treatment in centers of reference in Porto Alegre - RS

Introdução: Em 2005 o Ministério da Saúde do Brasil disponibilizou a enfuvirtida, o primeiro inibidor de fusão, uma nova classe de anti-retrovirais com ação extracelular. As dificuldades relatadas pelos primeiros usuários, em um dos centros de referência, e a carência de estudos envolvendo os usuários do Sistema Único de Saúde motivaram esta pesquisa. Objetivo: identificar os fatores de risco para baixa adesão ao tratamento com Enfuvirtida. Métodos: foram entrevistadas 37 pessoas de Porto Alegre, compreendendo a população total de usuários de enfuvirtida nesta cidade até o mês de outubro de 2006. Resultados: 27% dos pacientes já pensaram em desistir do tratamento, 22,2% referiram esquecimento de dose nos últimos 30 dias e 45,9% não souberam diferenciar HIV de aids. Os efeitos adversos locais ocorreram em todos os usuários, houve dor nos locais de aplicação em 81,1% dos casos, fato que não atrapalhou as atividades diárias (70,3%). Quanto às aplicações, 28,9% não tiveram a primeira dose supervisionada, 27% não realizaram massagem após as aplicações, 46% dos pacientes usavam regiões não orientadas pela enfermagem para aplicação, 29,7% acharam “difícil” encontrar um local para aplicar. Conclusão: o estudo reforça a necessidade do acompanhamento direto por um profissional de enfermagem para aplicação do medicamento, visto que os procedimentos podem parecer fáceis, mas requerem boa técnica para diluição, aspiração e aplicação a fim de diminuir os efeitos adversos locais, assim como as orientações sobre os cuidados após a aplicação.

Introduction: In 2005 the Ministry Health of Brazil provided Enfuvirtide, the first inhibitor of fusion, a new class of anti-retroviraes with extracellular action. The difficulties described by the first users, in one of the reference centers, and the lack of studies with the users of the Public Health Department, had motivated this research. Objective: to identify risk factors for low adhesion to the treatment with enfuvirtida. Methods: 37 people from Porto Alegre had been interviewed, the total population of users of enfuvirtide in this city until October, 2006. Results: had presented that 27% of the patients had already thought about giving up the treatment, 22,2% had forgotten to take the dose in the last 30 days and 45,9% do not know the difference between HIV and AIDS. The local adverse effect had occurred in all the users, pain in the application places were present in 81,1% of the cases, but it did not interfere in daily activities (70,3%). Concerning applications, 28,9% had not had a first supervised dose, 27% did not make a massage after the applications, 46% of the patients also used regions for application which were not guided by the nurses, 29,7% had had “difficulties” in finding a place to apply. Conclusion: the study strengthens the necessity of the direct accompaniment by a nursing professional, although the procedures can seem easy, they require good technique for dilution, aspiration and application to diminish the local adverse effects, as well as the orientation on the care after the application.