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1.
Eur J Pharm Biopharm ; 151: 162-170, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32311428

RESUMO

Bladder cancer is the fifth most common disease in the United States, and the treatment and alternatives for patients have not changed in the last decades. Silver nanoparticles (AgNP) have been used in the treatment of various cancer, mainly because of the antineoplastic activity; however, their use and the molecular mechanisms towards bladder cancer still unexplored. Therefore, this work aims to evaluate the in vitro and in vivo antitumoral mechanisms of biogenic silver nanoparticles synthesized from Fusarium sp. First, AgNP showed cytotoxicity in a dose- and time-response relationship and detailed analysis demonstrated the induction of cell death via apoptosis, also inhibiting cell migration and proliferation in bladder carcinoma cell line 5637. Next, it was evaluated the antitumoral activity of AgNP against non-muscle invasive bladder cancer (NMIBC). Bladder cancer was chemically induced with N-methyl-N-nitrosourea (MNU) on C57BL/6JUnib female mice and treated by intravesical route with AgNP concentrations of 0.5, 0.2, and 0.05 mg/mL. Finally, treatment with AgNP (0.05 mg/mL) led to 57.13% of tumor regression, with 14.28% of the animals showing normal urothelium, and 42.85% showing flat hyperplasia, considered to be a benign lesion. Overall, these findings demonstrated that AgNP might be a cost-effective alternative and promising candidate for the treatment of bladder cancer.

2.
Crit Rev Biotechnol ; 40(1): 15-30, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31658818

RESUMO

Nanotechnology has been proposed as an important tool and strategy for applying new products in agriculture at the nanometer scale in order to improve the food crop at sustainability and productivity levels for contributing with the agriculture security. Nanoparticles (NPs) have been planted as an intelligent material with a large contact surface per unit mass respect to bulk-products, allowing its effect to be exerted with greater efficiency in a specific point on a plant target. Currently, NPs have been studied to be applied to various species of monocotyledonous and dicotyledonous plants. Some NPs properties such as concentration, shape, size, composition and surface functionality have the ability to regulate the NPs growth effects on the plant during germination and seedling stages under controlled and field conditions. Furthermore, several studies have tried to explain the mechanism of uptake, translocation and accumulation of NPs inside the plant at the organ and cell level, but further studies are needed to determine specific mechanisms and exact action. Nevertheless, evaluation of the toxicity effects of NPs on physiological indexes of the plant is needed to determine the effective dose without producing adverse effects on the plant and food chain. It is noteworthy that studies have indicated that nanoparticles, regardless of their nature, can be efficient inducers of plant growth. However, a series of laboratory tests are required to optimize their application conditions and their specific physiological impact on plants. In this review, we summarize the knowledge about NPs application to induce plant growth to direct future studies in order to propose NPs for technological innovation.


Assuntos
Nanopartículas/administração & dosagem , Desenvolvimento Vegetal/efeitos dos fármacos , Nanopartículas/toxicidade , Nanotecnologia , Plantas/efeitos dos fármacos , Plantas/metabolismo
3.
Braz. dent. sci ; 23(3): 1-10, 2020.
Artigo em Inglês | LILACS, BBO - Odontologia | ID: biblio-1095370

RESUMO

Objectives: Reviewing information available about platelet-rich plasma (PRP) applied to dental treatments, introducing the general concept of PRP, as well as analyzing actual data about, and challenges faced by, the dental field. Data & sources: The current study analyzed the most informative publications about PRP application available in this field and gathered the maximum information about it as possible. Conclusions: PRP use, either alone or in association with other biomaterials, can significantly favor different fields such as tissue engineering, since it is an innovative technique that attracts the interest of clinicians and basic scientists. However, it is necessary conducting better designed and controlled experiments to enable successful tissue healing based on PRP use. Clinical significance: The current review can be used by clinicians as source of information about the actual rules and protocols adopted in the herein addressed field, besides providing specific examples of such applications. (AU)


Objetivos: Revisar as informações disponíveis sobre o plasma-rico em plaquetas (PRP) aplicado a tratamentos odontológicos, introduzir o conceito geral de PRP e analisar dados reais sobre os desafios enfrentados pelo campo odontológico. Dados e fontes: O presente estudo analisou as publicações mais informativas sobre a aplicação do PRP disponíveis neste campo e reuniu o máximo de informações possível. Conclusões: O uso do PRP, isoladamente ou em associação com outros biomateriais, pode favorecer significativamente diferentes campos, como a engenharia de tecidos, uma vez que é uma técnica inovadora que atrai o interesse de clínicos e cientistas básicos. No entanto, é necessário realizar experimentos mais bem projetados e controlados para permitir a cura bem-sucedida dos tecidos com base no uso do PRP. Significado clínico: A revisão atual pode ser usada pelos médicos como fonte de informações sobre as regras e protocolos atuais adotados no campo aqui tratado, além de fornecer exemplos específicos de tais aplicações.(AU)


Assuntos
Cirurgia Bucal , Fator de Crescimento Derivado de Plaquetas , Regeneração Tecidual Guiada Periodontal , Nanotecnologia , Plasma Rico em Plaquetas , Tratamento Dentário Restaurador sem Trauma
4.
Life Sci ; 242: 117185, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31862453

RESUMO

Colorectal cancer (CRC) is a multifactorial syndrome that drives to uncontrollable cell division, genetic alterations, and functional alteration. In the present work, we evaluated the immunomodulatory properties of P-mapa, a compound extracted from Aspergillus oryzae fungus, versus Fluorouracil (5-FU) treatment in chemically induced CRC. CRC was induced by DMH in F344 rats. Animals of treated groups receive weekly 15 mg/Kg of 5-FU or 5 mg/Kg of P-mapa, over 10 weeks. Tissues were stained for aberrant crypt foci (ACF) counting and histopathology evaluation, immunostained for TLR4 pathways and quantified for TNFα Cytokine assay. DMH was efficient to induce hyperplastic lesions and ACF. Both treatments reduced significantly ACF formation and tumor aggressiveness. Immunohistochemistry for TLR4 signaling reveals that both treatments had no effect over the TLR4-NFκB signaling pathway. On the other hand, both succeed in increase interferon signaling, with activation of the TRIF-IRF3 pathway and consequently inducing IFNγ synthesis. The present results show the immunomodulatory properties of P-mapa in chemically induced CRC model. P-mapa induced a significant increase in Type-I IFNs synthesis and subsequently immune cell recruitment, resulting in an increase of IFNγ concentration in colorectal mucosa and its inhibitory effects over tumoral growth. In this scenario, P-mapa showed an interesting antitumoral effect by inhibiting tumor growth.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias do Colo/tratamento farmacológico , Fatores Imunológicos/uso terapêutico , Ácidos Linoleicos/uso terapêutico , Ácidos Oleicos/uso terapêutico , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo , Focos de Criptas Aberrantes/patologia , Animais , Biopolímeros/uso terapêutico , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Ensaio de Imunoadsorção Enzimática , Fluoruracila/uso terapêutico , Masculino , Ratos , Ratos Endogâmicos F344 , Fator de Necrose Tumoral alfa/metabolismo
5.
Nanomedicine ; 24: 102130, 2019 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-31760163

RESUMO

Many studies have shown that silver nanoparticles (AgNP) induce oxidative stress, and it is commonly assumed that this is the main mechanism of AgNP cytotoxicity. Most of these studies rely on antioxidants to establish this cause-and-effect relationship; nevertheless, details on how these antioxidants interact with the AgNP are often overlooked. This work aimed to investigate the molecular mechanisms underlying the use of antioxidants with AgNP nanoparticles. Thus, we studied the molecular interaction between the thiol-antioxidants (N-acetyl-L-Cysteine, L-Cysteine, and glutathione) or non-thiol-antioxidants (Trolox) with chemically and biologically synthesized AgNP. Both antioxidants could mitigate ROS production in Huh-7 hepatocarcinoma cells, but only thiol-antioxidants could prevent the cytotoxic effect, directly binding to the AgNP leading to aggregation. Our findings show that data interpretation might not be straightforward when using thiol-antioxidants to study the interactions between metallic nanoparticles and cells. This artifact exemplifies potential pitfalls that could hinder the progress of nanotechnology and the understanding of the nanotoxicity mechanism.

6.
Biotechnol Lett ; 41(12): 1433-1437, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31650420

RESUMO

OBJECTIVES: To examine the synergistic antibacterial activity of violacein and silver nanoparticles (AgNPs) against ATCC bacteria, Staphylococcus aureus, Escherichia coli and two bacteria isolated from bovine mastitis. METHODS: Violacein from Chromobacterium violaceum and biogenic AgNPs from Fusarium oxysporum were evaluated in antimicrobial tests. RESULTS: E. coli isolates were not inhibited by violacein at concentrations up to 400 µM and they showed sensitivity for AgNPs between 62.5 and 250 µM. Staphylococcus aureus showed sensitivity to violacein with MIC of 200 µM, and the MIC with AgNPs between 250 µM and 125 µM. It was also tested the association between the two compounds through a concentration gradient and was observed the reduction of the MIC in the combination for both strains. CONCLUSION: The bactericidal effect of violacein against S. aureus was better when combined with AgNPs (synergistic).

7.
Front Microbiol ; 10: 1866, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31456780

RESUMO

Previously we reported the biosynthesis of intracellular cadmium sulfide quantum dots (CdS QDs) at low temperatures by the Antarctic strain Pseudomonas fragi GC01. Here we studied the role of volatile sulfur compounds (VSCs) in the biosynthesis of CdS QDs by P. fragi GC01. The biosynthesis of nanoparticles was evaluated in the presence of sulfate, sulfite, thiosulfate, sulfide, cysteine and methionine as sole sulfur sources. Intracellular biosynthesis occurred with all sulfur sources tested. However, extracellular biosynthesis was observed only in cultures amended with cysteine (Cys) and methionine (Met). Extracellular nanoparticles were characterized by dynamic light scattering, absorption and emission spectra, energy dispersive X-ray, atomic force microscopy, transmission electron microscopy, X-ray diffraction and X-ray photoelectron spectroscopy. Purified QDs correspond to cubic nanocrystals of CdS with sizes between 2 and 16 nm. The analysis of VSCs revealed that P. fragi GC01 produced hydrogen sulfide (H2S), methanethiol (MeSH) and dimethyl sulfide (DMS) in the presence of sulfate, Met or Cys. Dimethyl disulfide (DMDS) was only detected in the presence of Met. Interestingly, MeSH was the main VSC produced in this condition. In addition, MeSH was the only VSC for which the concentration decreased in the presence of cadmium (Cd) of all the sulfur sources tested, suggesting that this gas interacts with Cd to form nanoparticles. The role of MeSH and DMS on Cds QDs biosynthesis was evaluated in two mutants of the Antarctic strain Pseudomonas deceptionensis M1T: megL - (unable to produce MeSH from Met) and mddA - (unable to generate DMS from MeSH). No biosynthesis of QDs was observed in the megL - strain, confirming the importance of MeSH in QD biosynthesis. In addition, the production of QDs in the mddA - strain was not affected, indicating that DMS is not a substrate for the biosynthesis of nanoparticles. Here, we confirm a link between MeSH production and CdS QDs biosynthesis when Met is used as sole sulfur source. This work represents the first report that directly associates the production of MeSH with the bacterial synthesis of QDs, thus revealing the importance of different VSCs in the biological generation of metal sulfide nanostructures.

8.
Front Microbiol ; 10: 824, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31068912

RESUMO

Caseous lymphadenitis (CL) is an infectious and zoonotic disease characterized by the development of granulomas in the lymph nodes and internal organs of small ruminants. The etiological agent of this disease is Corynebacterium pseudotuberculosis, a Gram-positive and facultative intracellular bacterium. The conventional treatment for CL consists of drainage and chemical cauterization of the lesions using a 10% iodine solution. However, this type of treatment is not effective, due to iodine's cytotoxic profile and low antibacterial activity. Currently, silver nanoparticles (AgNPs) can be seen as an alternative treatment for CL due to their antimicrobial activity and wound healing effects. Therefore, the present study aimed to evaluate AgNPs as a post-surgical treatment for CL. Twenty-nine goats and sheep with clinical signs of CL were selected. Surgical intervention was performed to excise the caseous lesions. To treat the lesions, an ointment formulation based on AgNP mixed with natural waxes and oils was used in the experimental group, and the conventional treatment with 10% iodine was used in the control group. Bacteria were isolated from the excised caseous material. The animals were observed for 8 weeks after the surgical treatment, and blood samples were taken weekly. The surgical wounds of sheep treated with AgNP healed faster, and the surgical wound area was smaller during the observation period; the latter effect was also observed in goats. AgNP-treated animals also had less purulent discharge and less moisture in the surgical wounds. The AgNP-treated animals had lower leukocyte counts and lower titers of anti-C. pseudotuberculosis antibodies. There was no statistically significant difference between the groups with regard to the hemogram results. The results of the susceptibility testing of C. pseudotuberculosis strains (T1, 1002, FRC41, and VD57 strains) and clinical isolates to AgNPs showed growth inhibition, even at low concentrations. It can be concluded that post-surgical treatment of CL using the AgNP-based ointment may be a promising tool in the control of CL, through faster healing, decreased wound contamination, and no apparent toxic effects.

9.
World J Microbiol Biotechnol ; 35(6): 88, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31134435

RESUMO

In this work, the biosynthesis of silver nanoparticles by Galega officinalis extract using AgNO3 as a precursor was reported. The reaction parameters for the biosynthesis and efficiency in their antimicrobial control against Escherichia coli, Staphylococcus aureus and Pseudomonas syringae were determined. For biosynthesis, a central composite design combined with response surface methodology was used to optimize the process parameters (pH, AgNO3 and extract concentration), and the design was assessed through the size distribution, zeta potential and polydispersity index of the nanoparticles. The results demonstrated that at pH 11, 1.6 mM of AgNO3 and 15% vv-1 of G. officinalis extract were the optimal reaction parameters. Transmission electron microscope (TEM) images and X-ray diffraction (XRD) confirmed the formation of small spherical silver nanoparticles. Antimicrobial assays showed a high inhibitory effect against E. coli, S. aureus and P. syringae, and that effect was larger with silver nanoparticles of a smaller size (23 nm). This work demonstrates that G. officinalis extract is a feasible medium for the synthesis of silver nanoparticles and that the control of the reaction parameters can determine the nanoparticle characteristics and therefore their antimicrobial effectiveness.


Assuntos
Anti-Infecciosos/metabolismo , Química Verde/métodos , Nanopartículas Metálicas/química , Prata/química , Antibacterianos/química , Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Escherichia coli/efeitos dos fármacos , Galega/química , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Transmissão , Tamanho da Partícula , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química , Pseudomonas syringae/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Difração de Raios X
10.
Mutat Res ; 841: 8-13, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31138412

RESUMO

Graphene is a two-dimensional (2D) monolayer of carbon atoms, tightly packed, forming a honey comb crystal lattice, with physical, chemical, and mechanical properties greatly used for energy storage, electrochemical devices, and in nanomedicine. Many studies showed that nanomaterials have side-effects on health. At present, there is a lack of information regarding graphene and its derivatives including their cardiotoxic properties. The aim of the present study was to evaluate the toxicity of nano-graphene oxide (nano-GO) in the rat cardiomyoblast cell line H9c2 and the involvement of oxidative processes. The cell viability was evaluated with the fluorescein diacetate (FDA)/propidium iodide (PI) and in the trypan blue exclusion assay, furthermore mitochondrial membrane potential and production of free radicals were measured. Genotoxicity was evaluated in comet assay and low molecular weight DNA experiment. Reduction of cell viability with 20, 40, 60, 80, and 100 µg/mL nano-GO was observed after 24 h incubation. Besides, nano-GO induced a mitochondrial hyperpolarization and a significant increase of free radicals production in the same concentrations. DNA breaks were observed at 40, 60, 80, and 100 µg/mL. This DNA damage was accompanied by a significant increase in LMW DNA only at 40 µg/mL. In conclusion, the nano-GO caused cardiotoxicity in our in vitro model, with mitochondrial disturbances, generation of reactive species and interactions with DNA, indicating the importance of the further evaluation of the safety of nanomaterials.

11.
Int J Food Microbiol ; 291: 79-86, 2019 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-30476736

RESUMO

Aspergillus spp. are ubiquitous fungi that grow on stored grains. Some species produce toxins that can harm human and animal health, leading to hepato- and nephrotoxicity, immunosuppression and carcinogenicity. Major fungicides used to prevent fungal growth may be toxic to humans and their repeated use over time increases levels of resistance by microorganisms. Nanotechnology is an emerging field that allows use of antimicrobial compounds in a more efficient manner. In this study, was evaluated the antifungal activity of biogenic silver nanoparticles (AgNPs, synthesized by fungi) and simvastatin (SIM, a semi-synthetic drug), alone and in combination against three toxigenic species belonging to the genera Aspergillus section Flavi (Aspergillus flavus, Aspergillus nomius and Aspergillus. parasiticus) and two of section Circumdati (Aspergillus ochraceus and Aspergillus melleus). SIM exhibited a MIC50 of 78 µg/mL against species of Section Flavi and a MIC50 of 19.5 µg/mL against species of Section Circumdati. The MIC50 of AgNPs against Aspergillus flavus, Aspergillus nomius and Aspergillus parasiticus was 8 µg/mL, while the MIC50 was 4 µg/mL against Aspergillus melleus and Aspergillus ochraceus. Checkerboard assay showed that these compounds, used alone and in combination, have synergistic and additive effects against toxicogenic species of Aspergillus. Analysis by SEM gives an idea of the effect of SIM and AgNPs alone and in combination on spore germination and vegetative growth. Ultrastructural analysis revealed that spore germination was prevented, or aberrant hyphae were formed with multilateral branches upon treatment with SIM and AgNPs. These results reveal potential benefits of using combination of AgNPs and SIM to control fungal growth.


Assuntos
Antifúngicos/farmacologia , Aspergillus/efeitos dos fármacos , Nanopartículas Metálicas/química , Prata/farmacologia , Sinvastatina/farmacologia , Antifúngicos/química , Aspergillus flavus/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Microscopia Eletrônica de Varredura , Prata/química
12.
Nanotoxicology ; 13(3): 326-338, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30477371

RESUMO

The increasing use of silver nanoparticles (AgNPs) in consumer products raises the risk of human toxicity. Currently, there are no therapeutic options or established treatment protocols in cases of AgNPs intoxication. We demonstrated previously that thiol antioxidants compounds can reverse the cytotoxicity induced by AgNPs in Huh-7 hepatocarcinoma cells. Here, we investigated the use of N-acetylcysteine (NAC) against the systemic toxic effects of AgNPs (79.3 nm) in rats. Biochemical, histopathological, hematological, and oxidative parameters showed that a single intravenous injection of AgNPs (5 mg/kg b.w.) induced deleterious effects such as hepatotoxicity, potentially as a result of AgNPs accumulation in the liver. Treatment with a single intraperitoneal injection of NAC (1 g/kg b.w.) one hour after AgNPs exposure significantly attenuated all toxic effects evaluated and altered the bioaccumulation and release patterns of AgNPs in rats. The findings show that NAC may be a promising candidate for clinical management of AgNPs intoxication.


Assuntos
Acetilcisteína/farmacologia , Antioxidantes/farmacologia , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Fígado/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Prata/toxicidade , Animais , Humanos , Injeções Intraperitoneais , Injeções Intravenosas , Masculino , Nanopartículas Metálicas/química , Ratos , Prata/química
13.
Pharmaceutics ; 10(4)2018 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-30441802

RESUMO

Dibucaine (DBC) is among the more potent long-acting local anesthetics (LA), and it is also one of the most toxic. Over the last decades, solid lipid nanoparticles (SLN) have been developed as promising carriers for drug delivery. In this study, SLN formulations were prepared with the aim of prolonging DBC release and reducing its toxicity. To this end, SLN composed of two different lipid matrices and prepared by two different hot-emulsion techniques (high-pressure procedure and sonication) were compared. The colloidal stability of the SLN formulations was tracked in terms of particle size (nm), polydispersity index (PDI), and zeta potential (mV) for 240 days at 4 °C; the DBC encapsulation efficiency was determined by the ultrafiltration/centrifugation method. The formulations were characterized by differential scanning calorimetry (DSC), electron paramagnetic resonance (EPR), and release kinetic experiments. Finally, the in vitro cytotoxicity against 3T3 fibroblast and HaCaT cells was determined, and the in vivo analgesic action was assessed using the tail flick test in rats. Both of the homogenization procedures were found suitable to produce particles in the 200 nm range, with good shelf stability (240 days) and high DBC encapsulation efficiency (~72⁻89%). DSC results disclosed structural information on the nanoparticles, such as the lower crystallinity of the lipid core vs. the bulk lipid. EPR measurements provided evidence of DBC partitioning in both SLNs. In vitro (cytotoxicity) and in vivo (tail flick) experiments revealed that the encapsulation of DBC into nanoparticles reduces its intrinsic cytotoxicity and prolongs the anesthetic effect, respectively. These results show that the SLNs produced are safe and have great potential to extend the applications of dibucaine by enhancing its bioavailability.

14.
Langmuir ; 34(44): 13296-13304, 2018 11 06.
Artigo em Inglês | MEDLINE | ID: mdl-30299102

RESUMO

Dibucaine (DBC) is one of the most potent long-acting local anesthetics, but it also has significant toxic side effects and low water solubility. Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have been proposed as drug-delivery systems to increase the bioavailability of local anesthetics. The purpose of the present study was to characterize SLNs and NLCs composed of cetyl palmitate or myristyl myristate, a mixture of capric and caprylic acids (for NLCs only) plus Pluronic F68 prepared for the encapsulation of DBC. We intended to provide a careful structural characterization of the nanoparticles to identify the relevant architectural parameters that lead to the desirable biological response. Initially, SLNs and NLCs were assessed in terms of their size distribution, morphology, surface charge, and drug loading. Spectroscopic techniques (infrared spectroscopy and electron paramagnetic resonance, EPR) plus small-angle X-ray scattering (SAXS) provided information on the interactions between nanoparticle components and their structural organization. The sizes of nanoparticles were in the 180 nm range with low polydispersity and negative zeta values (-25 to -46 mV). The partition coefficient of DBC between nanoparticles and water at pH 8.2 was very high (>104). EPR (with doxyl-stearate spin labels) data revealed the existence of lamellar arrangements inside the lipid nanoparticles, which was also confirmed by SAXS experiments. Moreover, the addition of DBC increased the molecular packing of both SLN and NLC lipids, indicative of DBC insertion between the lipids, in the milieu assessed by spin labels. Such structural information brings insights into understanding the molecular organization of these versatile drug-delivery systems which have already demonstrated their potential for therapeutic applications in pain control.


Assuntos
Anestésicos Locais/química , Dibucaína/química , Portadores de Fármacos/química , Nanopartículas/química , Espectroscopia de Ressonância de Spin Eletrônica , Miristatos/química , Nanopartículas/ultraestrutura , Palmitatos/química , Tamanho da Partícula , Poloxâmero/química , Espalhamento a Baixo Ângulo , Difração de Raios X
15.
Tissue Cell ; 52: 17-27, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29857824

RESUMO

This study describes the effects of a promising therapeutic alternative for non-muscle invasive bladder cancer (NMIBC) based on Bacillus Calmette-Guerin (BCG) intravesical immunotherapy combined with Platelet-rich plasma (PRP) in an animal model. Furthermore, this study describes the possible mechanisms of this therapeutic combination involving Toll-like Receptors (TLRs) 2 and 4 signaling pathways. NMIBC was induced by treating female Fischer 344 rats with N-methyl-N-nitrosourea (MNU). After treatment with MNU, the animals were distributed into four experimental groups: Control (without MNU) group, MNU (cancer) group, MNU + PRP group, MNU + BCG group and MNU + PRP + BCG group. Our results demonstrated that PRP treatment alone or associated with BCG triggered significant cytotoxicity in bladder carcinoma cells (HTB-9). Animals treated with PRP associated to BCG clearly showed better histopathological recovery from the cancer state and decrease of urothelial neoplastic lesions progression in 70% of animals when compared to groups that received the same therapies administered singly. In addition, this therapeutic association led to distinct activation of immune system TLRs 2 and 4-mediated, resulting in increased MyD88, TRIF, IRF3, IFN-γ immunoreactivities. Taken together, the data obtained suggest that interferon signaling pathway activation by PRP treatment in combination with BCG immunotherapy may provide novel therapeutic approaches for non-muscle invasive bladder cancer.


Assuntos
Carcinoma de Células de Transição/patologia , Mycobacterium bovis , Plasma Rico em Plaquetas , Neoplasias da Bexiga Urinária/patologia , Animais , Feminino , Humanos , Sistema Imunitário/efeitos dos fármacos , Ratos , Ratos Endogâmicos F344
16.
Eur J Pharmacol ; 826: 158-168, 2018 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-29501865

RESUMO

Nitric oxide (NO) is an endogenous molecule that plays pivotal physiological and pathophysiological roles, particularly in cancer biology. Generally, low concentrations of NO (pico- to nanomolar range) lead to tumor promotion. In contrast, high NO concentrations (micromolar range) have pro-apoptotic functions, leading to tumor suppression, and in this case, NO is involved in immune surveillance. Under oxidative stress, inducible NO synthase (iNOS) produces high NO concentrations for antineoplastic activities. Prostate and bladder cancers are the most commonly detected cancers in men, and are related to cancer death in males. This review summarizes the state of the art of NO/NO donors in combating prostate and bladder cancers, highlighting the importance of NO donors in cancer treatment, and the limitations and challenges to be overcome. In addition, the combination of NO donors with classical therapies (radio- or chemotherapy) in the treatment of prostate and bladder cancers is also presented and discussed. The combination of NO donors with conventional anticancer drugs is reported to inhibit tumor growth, since NO is able to sensitize tumor cells, enhancing the efficacy of the traditional drugs. Although important progress has been made, more studies are still necessary to definitely translate the administration of NO donors to clinical sets. The purpose of this review is to inspire new avenues in this topic.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doadores de Óxido Nítrico/uso terapêutico , Óxido Nítrico/metabolismo , Neoplasias da Próstata/terapia , Neoplasias da Bexiga Urinária/terapia , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Quimiorradioterapia/métodos , Humanos , Masculino , Doadores de Óxido Nítrico/farmacologia , Óxido Nítrico Sintase Tipo II/metabolismo , Estresse Oxidativo , Neoplasias da Próstata/patologia , Resultado do Tratamento , Neoplasias da Bexiga Urinária/patologia
17.
Carbohydr Polym ; 181: 514-527, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29254002

RESUMO

Cellulose nanocrystals (CNCs) are crystalline nanoparticles that present myriad applications. CNCs are produced from a variety of renewable sources, and they can be chemically modified. Although there are promising perspectives for introducing CNCs into pharmaceutical formulations, prior to achieving commercial products the influence of many parameters such as extraction and toxicity of the resulting products must be revealed. Since there is great physicochemical flexibility in the steps of obtaining and conjugating CNCs, there are uncountable and complex outcomes from the interactions of those parameters. We present a discussion that helps to unveil the whole panorama on the use of CNCs as drug delivery systems. The methods of producing CNCs are correlated to the resulting nanotoxicity from the cellular to organism level. This review points to relevant concerns that must be overcome to attain safe use of these nanostructures. We also discuss the patents and commercially available products based on CNCs.

18.
Acta Trop ; 178: 46-54, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29111137

RESUMO

American Cutaneous Leishmaniasis (ACL) is a zoonosis caused by Leishmania protozoa. The ACL chemotherapy available is unsatisfactory motivating researches to seek alternative treatments. In this study, we investigated the action of biogenic silver nanoparticle (AgNp-bio) obtained from Fusarium oxysporium, against Leishmania amazonensis promastigote and amastigote forms. The AgNp-bio promastigote treatment results in promastigote death leading to apoptosis-like events due an increased production of reactive oxygen species (ROS), loss of mitochondrial integrity, phosphatidylserine exposure and damage on promastigotes membrane. In L. amazonensis infected macrophages, AgNp-bio treatment was still able to reduce the percentage of infected macrophages and the amount of amastigotes per macrophage, consequently, the amount of promastigotes recovered. This leishmanicidal effect was also accompanied by a decrease in the levels of ROS and nitric oxide. By observing the ultrastructural integrity of the intracellular amastigotes, we found that the AgNp-bio treatment made a significant damage, suggesting that the compound has a direct effect on intracellular amastigotes. These results demonstrated that AgNp-bio had a direct effect against L. amazonensis forms and acted on immunomodulatory ability of infected macrophages, reducing the infection without inducing the synthesis of inflammatory mediators, which continuous stimulation can generate and aggravate leishmaniotic lesions. Overall, our findings suggest that the use of AgNp-bio stands out as a new therapeutic option to be considered for further in vivo investigations representing a possible treatment for ACL.


Assuntos
Antiprotozoários/uso terapêutico , Apoptose/efeitos dos fármacos , Leishmania/efeitos dos fármacos , Leishmaniose/tratamento farmacológico , Nanopartículas Metálicas/uso terapêutico , Prata/uso terapêutico , Animais , Camundongos , Camundongos Endogâmicos BALB C
19.
Braz. dent. sci ; 21(1): 96-103, 2018. ilus, tab
Artigo em Inglês | LILACS, BBO - Odontologia | ID: biblio-881930

RESUMO

Objective: This study evaluated the effects of the incorporation of silver nanoparticles (AgNPs) obtained from Fusarium oxysporum on heat-activated acrylic resin (HAAR) and their influence on resin's surface roughness, hardness, color alteration and antimicrobial capacity against Candida albicans. Material and Methods: For this, 50 discs of HAAR (2x5 mm) were produced and divided into three groups, Control: HAAR; Ag1: HAAR plus 0.539 mg of AgNPs; and Ag2: HAAR plus 1.1 mg of AgNPs. Knopp hardness (HK), surface roughness (Ra and Rz) and color alteration according to the CIE Lab were measured. Specimens were then evaluated in vitro with regard to C. albicans biofilm formation through formed colony count (CFU/mL). Scanning Electron Microscopy (SEM) and Atomic force microscopy (AFM) analyses were performed. Results: The addition of AgNPs of both concentrations changed Ra, Rz and HK significantly. There was statistically significant difference for L (p=0.00); a*(p=0.00) and b*(p=0.00) parameters. There were no differences between Ag1 and Ag2 biofilm formation, but the comparison of both with the control group presented a significant reduction (p=0.0091) on biofilm formation. SEM and AFM images showed no signs of NPs clustering. Conclusion: It can be concluded tha AgNPs incorporation in HAAR was effective in reducing C. albicans activity, with a slight change in color and hardness of the material, being effective therefore, in regions such as the dental prostheses palate, which have lesser aesthetic appeal. (AU)


Objetivo: Este estudo avaliou os efeitos da incorporação de nanopartículas de prata (AgNPs) obtidas a partir de Fusarium oxysporum em resina acrílica ativada termicamente (RAAT) e sua influência na rugosidade, dureza, cor e capacidade antimicrobiana contra Candida albicans. Material e Métodos: Para isso, 50 discos de RAAT (2x5 mm) foram produzidos e divididos em três grupos, Controle: RAAT; Ag1: RAAT com 0,539 mg de AgNPs; e Ag2: RAAT com 1,1 mg de AgNPs. Foram medidas a dureza Knopp (DK), a rugosidade superficial (Ra e Rz) e a alteração da cor de acordo com o sistema CIE Lab. As amostras foram então avaliadas in vitro em relação à formação de biofilme de C. albicans através da contagem de unidades formadoras de colônia (UFC / mL). Foram realizadas análises de Microscopia Eletrônica de Varredura (MEV) e Microscopia de Força Atômica (AFM). Resultados: A adição de AgNPs de ambas as concentrações alterou significativamente Ra. Rz e DK. Houve diferença estatisticamente significativa para os parâmetros L (p = 0,00); a * (p = 0,00) e b * (p = 0,00). Não houve diferenças entre a formação de biofilme Ag1 e Ag2, mas a comparação entre ambos com o grupo controle apresentou redução significativa (p = 0,0091) na formação de biofilmes. As imagens de MEV e AFM não mostraram sinais de agrupamento de NPs. Conclusão: Pode-se concluir que a incorporação de AgNP no RAAT foi eficaz na redução da atividade de C. albicans, com uma discreta alteração na cor e dureza do material, sendo efetiva, portanto, em regiões linguais de próteses dentárias, que possuem menor apelo estético. (AU)


Assuntos
Resinas Acrílicas , Anti-Infecciosos , Prata
20.
Curr Pharm Des ; 2017 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-29141536

RESUMO

BACKGROUND: Lipid nanoparticles are considered one of the most promising systems for controlled release of therapeutic molecules highly hydrophobic and with low biodisponibility. Solid lipid nanoparticles and nanostructured lipids carriers are widely seen as the workhorses of drug delivery systems because of low toxicity, enhanced encapsulation capacity, controlled drug kinetic release, easy tailoring and targeting and practicable scale up. CONCLUSIONS: A new generation of hybrid lipid nanoparticles has emerged by combining the lipidic properties with polymers, proteins and metallic structures. The main features of hybrid lipid nanoparticles including popular methods for synthesis and characterization, biological and toxicological properties, administration routes, drug encapsulation strategies, tailoring and targeting, and potential systems for use in biomedicine are described in the present review.

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