RESUMO
Vorinostat (VST) is a chemotherapeutic agent administrated for various types of cancers. However, it suffers from side effects and chemoresistance that reduce its application. Different nanoniosomes comprised Span 20, 60, 65 and 80 were prepared by the thin film hydration method and loaded with VST. The nanoniosomes were physicochemically characterized using particle size analysis and field emission scanning electron microscopy. The best formulation that was prepared using Span 65 (VST-NN-S65) included vesicle size of 127 nm with a narrow size distribution. VST-NN-S65 had an entrapment efficiency and loading capacity of 81.3 ± 5.1 and 32.0 ± 3.9 %, respectively. Drug release rate measurements showed that 90 % of VST was liberated within 1 h. Cytotoxicity assessments of VST-NN-S65 in HeLa and MCF7 cells indicated significant improvement in the effectiveness of VST, compared to the VST suspension. For VST-NN-S65, IC50 values of 26.3 and 6.6 µg mL-1 were obtained for HeLa and MCF7 cell lines, respectively. In situ apoptosis detection by the TUNEL assay revealed that apoptosis mainly occurred in the cell lines.
Assuntos
Antineoplásicos , Apoptose , Portadores de Fármacos , Ácidos Hidroxâmicos , Lipossomos , Tamanho da Partícula , Vorinostat , Humanos , Vorinostat/farmacologia , Vorinostat/administração & dosagem , Vorinostat/química , Antineoplásicos/farmacologia , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Células HeLa , Células MCF-7 , Apoptose/efeitos dos fármacos , Ácidos Hidroxâmicos/química , Ácidos Hidroxâmicos/administração & dosagem , Ácidos Hidroxâmicos/farmacologia , Portadores de Fármacos/química , Nanopartículas/química , Liberação Controlada de Fármacos , Sobrevivência Celular/efeitos dos fármacosRESUMO
Background: Aggressive periodontitis is a severe form of periodontal disease characterized by rapid tissue destruction and tooth loss. The optimal treatment approach for managing this condition remains a topic of debate. Materials and Methods: A retrospective cohort study was conducted, involving patients diagnosed with aggressive periodontitis who received either surgical or non-surgical treatment between 2010 and 2020. Clinical and radiographic data were collected at baseline and regular intervals over a 5-year follow-up period. Surgical interventions included flap surgery, guided tissue regeneration, and bone grafting, while non-surgical treatments comprised scaling and root planning with or without adjunctive antibiotics. The primary outcomes assessed included changes in probing depth, clinical attachment level, tooth loss, and patient-reported quality of life measures. Results: A total of 120 patients were included in the study, with 60 patients in each treatment group. The surgical group demonstrated significantly greater reductions in probing depth and gains in clinical attachment level compared to the non-surgical group (P < 0.05). Tooth loss was significantly lower in the surgical group over the 5 years (P < 0.01). Patient-reported outcomes also favored the surgical group, with improved oral health-related quality of life. However, the surgical group had a higher incidence of postoperative complications. Conclusion: This study suggests that periodontal surgery yields superior long-term outcomes in the management of aggressive periodontitis compared to non-surgical treatment.
RESUMO
The utilization of ultrasound (US) to activate sonosensitizers for sonodynamic therapy (SDT) has faced challenges such as low activation efficiency and limited therapeutic outcomes, which have hampered its clinical applications. In this study, a nanohybrid of titanium dioxide-gold-polyethylene glycol-curcumin (TiO2-Au-PEG-Cur NH), as a novel US sensitizer, was synthesized, characterized, and applied for SDT of HeLa cancer cells in 2D monolayer model, and also a 3D spheroid model to bridge the gap between 2D cell culture and in vivo future studies. TiO2-Au-PEG-Cur NH contained TiO2 nanoparticles of 36 ± 11 nm in diameter, PEG-curcumin as a filler, and gold nanoparticles of 21 ± 7 nm in diameter with a high purity and a 35:17 of Ti:Au ratio (W/W), and it had a band gap of 2.4 eV, a zeta potential of -23 ± 7 mV, high stability upon US radiation cycles as well as one year storage. SDT of HeLa cells using TiO2-Au-PEG-Cur NH was investigated in the courses of cytotoxicity assessment in vitro, reactive oxygen species (ROS) generation capability, colony formation, cell migration, and the way to form spheroid. IC50 values of 122 and 38 µg mL-1 were obtained for TiO2-Au-PEG-Cur NH without and with US radiation, respectively. TiO2-Au-PEG-Cur NH not only exhibited an inherent capacity to generate ROS, but also represented an excellent therapeutic performance on the cancer cells through ROS generation and enhanced inhibitory effects on cell migration and spheroid formation.
Assuntos
Curcumina , Nanopartículas Metálicas , Nanopartículas , Neoplasias , Humanos , Curcumina/farmacologia , Células HeLa , Polietilenoglicóis/farmacologia , Ouro/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Titânio/farmacologia , Linhagem Celular TumoralRESUMO
It is estimated that there are 400000 new cases of visceral leishmaniasis each year, with about 30,000 deaths. Therefore, detection of this pathogen and its species is highly vital for overall health of the community. In the present research, a DNA-based biosensor, namely genosensor, was introduced for detection of genomic DNA of Leishmania infantum. The genosensor was fabricated based on the transduction of cadmium sulfide nanosheets and recognition of a particular single stranded DNA sequence, and worked in label-, marker-, tag- and PCR-free manners. Impedimetric measurements were performed in a wide range of frequency (recording Nyquist diagrams) without applying external force (working at open circuit potential) upon hybridization of DNA targets with the cadmium sulfide nanosheets surface-immobilized probe. The genosensor detected the complementary DNA strand in a concentration range of 1.0 × 10-14 to 1.0 × 10-6 mol L-1 and a detection limit (DL) of 0.81 fmol L-1 (6.5 fg mL-1), and genomic DNA of Leishmania infantum in a concentration range of 5-50 ng µL-1 and a DL of 1.2 ng µL-1. The genosensor had a very good selectivity, fabrication reproducibility and stability, and was applicable for practical applications.
Assuntos
Técnicas Biossensoriais , Compostos de Cádmio/química , Espectroscopia Dielétrica , Técnicas Eletroquímicas , Leishmania infantum/isolamento & purificação , Nanoestruturas/química , Sulfetos/químicaRESUMO
Prostate cancer is one of the most dangerous and deadly cancers in elderly men. Early diagnosis using prostate-specific antigen (PSA) facilitates disease detection, management and treatment. Biosensors have recently been used as sensitive, selective, inexpensive and rapid diagnostic tools for PSA detection. In this review, a variety of PSA biosensors such as aptasensors, peptisensors and immunesensors are highlighted. These use aptamers, peptides and antibodies in the biorecognition element, respectively, and can detect PSA with very high sensitivity via electrochemical, electrochemiluminescence, fluorescence and surface-enhanced Raman spectroscopy. To improve the sensitivity of most of these PSA biosensors, different nanostructured materials have played a critical role.
Assuntos
Técnicas Biossensoriais , Nanoestruturas , Neoplasias da Próstata , Idoso , Humanos , Masculino , Nanotecnologia , Antígeno Prostático Específico , Neoplasias da Próstata/diagnósticoRESUMO
A highly simple, sensitive, specific and low-cost electrochemical apta-cyto-sensor for determination of circulating human MDA-MB-231 breast cancer cells was fabricated. Non-spherical nanoparticles of gold were electro-deposited in the presence of ethosuximide as a shape directing and size controlling agent. The nanoparticles had dimensions ranging 50-150â¯nm, and covered the underlying surface with a roughness factor of 8.03. The Non-spherical nanoparticles were then employed as the apta-cyto-sensor transducer. A 83-mer DNA aptamer that is specific to capturing the cell surface proteins was immobilized on the transducer surface, and binding with the cells was followed using the ferro/ferricyanide redox marker. The aptamer was immobilized within â¼200â¯min on the transducer surface. The cells were quantified with an equation of regression of ΔIp(µA) = (1.028⯱â¯0.027) log (C (cell mL-1)) + (0.2199⯱â¯0.0944), a sensitivity of 1.028⯵A (log (concentration / cell mL-1))-1 and a quantitation limit of 2 cell mL-1, in a concentration range of 5 to 2â¯×â¯106 cell mL-1. The apta-cyto-sensor selectivity was also evaluated toward AsPC-1, Calu-6, HeLa, MCF-7 and melanoma B16/F10 cell lines. The apta-cyto-sensor had a fabrication reproducibility of 4.2%, regeneration capability of 5.1%, a stability of 35 days, and a potential application for the detection of MDA-MB-231 cells in the spiked blood serum samples with a sensitivity of 0.8975⯵A (log (concentration / cell mL-1))-1 and a quantitation limit of 5 cell mL-1, in a concentration range of 10 to 1â¯×â¯103 cell mL-1. The apta-cyto-sensor would be applicable for breast cancer diagnosis at early stage.
Assuntos
Técnicas Biossensoriais/métodos , Neoplasias da Mama/tratamento farmacológico , Técnicas Eletroquímicas/métodos , Ouro/administração & dosagem , Nanopartículas Metálicas/administração & dosagem , Aptâmeros de Nucleotídeos/administração & dosagem , Linhagem Celular Tumoral , DNA/administração & dosagem , Eletrodos , Feminino , Células HeLa , Humanos , Limite de Detecção , Células MCF-7 , Melanoma Experimental , Reprodutibilidade dos TestesRESUMO
Some of microorganisms are potential pathogens that can be infectious agents under some circumstances, and development of new detection methods of the pathogens is of high interest. In the present study, an Enterococcus faecalis (E. faecalis) DNA biosensor (ef-biosensor) was fabricated to quantify the bacterium genome. A specific E. faecalis DNA probe was selected from 16S rRNA sequence of E. faecalis and immobilized on a gold electrode surface in an optimized time to fabricate the ef-biosensor. The ef-biosensor detected a synthetic target of the probe with a detection limit of 3.3â¯amolâ¯L-1 and with a nice selectivity to resolve from one-, two- and three-base mismatched sequences. In addition, the bacterium genomic DNA was quantified with a detection limit of 7.1â¯×â¯10-9â¯ngâ¯mL-1 in a concentration range of 1.1â¯×â¯10-7 to 1.1â¯ngâ¯mL-1. The ef-biosensor had a long time stability, good fabrication reproducibility and good regeneration ability. The ef-biosensor was successfully applied for E. faecalis detection in human samples.
Assuntos
Técnicas Biossensoriais/métodos , Sondas de DNA/química , DNA Bacteriano/análise , Enterococcus faecalis/isolamento & purificação , Infecções por Bactérias Gram-Positivas/microbiologia , RNA Ribossômico 16S/química , Sequência de Bases , Sondas de DNA/genética , DNA Bacteriano/genética , Técnicas Eletroquímicas/métodos , Enterococcus faecalis/genética , Infecções por Bactérias Gram-Positivas/diagnóstico , Humanos , Limite de Detecção , RNA Ribossômico 16S/genética , Reprodutibilidade dos TestesRESUMO
Cutaneous leishmaniasis is the most common form of leishmaniasis caused by different species of Leishmania parasites. The emergence of resistance, toxicity, long term treatment, high cost of the current drugs, and intracellular nature of the parasite are the major difficulties for the treatment of leishmaniasis. Although the therapeutic effect of paromomycin (PM) on leishmaniasis has been investigated in different studies, it has a low oral absorption and short half-life, leading to a decreased drug efficacy. Therefore, new and targeted carriers with no such problems are needed. In the present study, PM was loaded into chitosan (CS) nanoparticles accompanied by targeting to macrophages (as the host of Leishmania parasite). PM-loaded into mannosylated CS (MCS) nanoparticles using dextran (PM-MCS-dex-NPs) was prepared by ionic gelation and then characterized. The particle size and zeta potential of PM-MCS-dex-NPs were obtained as 246â¯nm and +31 mV, respectively. Mannosylation of CS was qualitatively evaluated by Fourier-transform infrared spectroscopy and quantitatively measured by CHNO elemental analysis; also, a mannosylation level of 17% (w) was attained. Encapsulation efficiency (EE), drug release profile, and THP-1 cell uptake potential were determined. A value of 83.5% for EE and a higher release rate in acidic media were achieved. THP-1 cell uptake level of PM-MCS-dex-NPs after 6â¯h was Ë2.8 and Ë3.9 times of non-mannosylated CS nanoparticles (PM-CS-dex-NPs) and PM aqueous solution, respectively. In vitro cell cytotoxicity and promastigote and amastigote viabilities were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Half-maximal inhibitory concentration values toward the THP-1 cells for PM aqueous solution, Glucantim, PM-CS-dex-NPs, and PM-MCS-dex-NPs after 48â¯h were obtained as 1846⯱â¯158, 1234⯱â¯93, 784⯱â¯52 and 2714⯱â¯126⯵g mL-1, respectively. Half-maximal inhibitory concentration values toward the promastigotes for PM aqueous solution, Glucantim, PM-CS-dex-NPs, and PM-MCS-dex-NPs after 48â¯h were obtained as 105.0⯱â¯14.0, 169.5⯱â¯9.8, 65.8⯱â¯7.3 and 17.8⯱â¯1.0⯵g mL-1, respectively. Selectivity (therapeutic) indices for PM aqueous solution, Glucantim, PM-CS-dex-NPs and PM-MCS-dex-NPs after 48â¯h were obtained as 24.6, 17.5, 3.7 and 214, respectively. The parasite burden in THP-1 cells after 48â¯h treatment with PM aqueous solution, Glucantim, PM-CS-dex-NPs, and PM-MCS-dex-NPs at a typical concentration of 20⯵gâ¯mL-1 were 71.78, 69.94, 83.14 and 33.41%, respectively. While the effect of PM-CS-dex-NPs was more salient on amastigotes, PM-MCS-dex-NPs effectively affected both stages of the parasite, especially the amastigote one. This indicated that the mannosylated formulation acts as a targeted delivery system. The findings of this study revealed that this novel targeted formulation represented a strong anti-leishmanial activity.
RESUMO
Cutaneous leishmaniasis is the most common form of leishmaniasis caused by different species of Leishmania parasites. The emergence of resistance, toxicity, long term treatment, high cost of the current drugs, and intracellular nature of the parasite are the major difficulties for the treatment of leishmaniasis. Although the therapeutic effect of paromomycin (PM) on leishmaniasisLeishmania parasite). PM-loaded into mannosylated CS (MCS) nanoparticles using dextran (PM-MCS-dex-NPs) was prepared by ionic gelation and then characterized. The particle size and Zeta potential of PM-MCS-dex-NPs were obtained as 246â¯nm andâ¯+â¯31 mV, respectively. Mannosylation of CS was qualitatively evaluated by Fourier-transform infrared spectroscopy and quantitatively measured by CHNO elemental analysis; also, a mannosylation level of 17% (w) was attained. Encapsulation efficiency (EE), drug release profile, and THP-1 cell uptake potential were determined. A value of 83.5% for EE and a higher release rate in acidic media were achieved. THP-1 cell uptake level of PM-MCS-dex-NPs after 6â¯h was Ë2.8 and Ë3.9 times of non-mannosylated CS nanoparticles (PM-CS-dexIn vitroGlucantim, PM-CS-dex-NPs, and PM-MCS-dex-NPs after 48â¯h were obtained as 1846⯱â¯158, 1234⯱â¯93, 784⯱â¯52 and 2714⯱â¯126⯵g mL-1Glucantim, PM-CS-dex-NPs, and PM-MCS-dex-NPs after 48â¯h were obtained as 105.0⯱â¯14.0, 169.5⯱â¯9.8, 65.8⯱â¯7.3 and 17.8⯱â¯1.0⯵g mL-1Glucantim, PM-CS-dex-NPs and PM-MCS-dexGlucantim, PM-CS-dex-NPs, and PM-MCS-dex-NPs at a typical concentration of 20⯵gâ¯mL-1 were 71.78, 69.94, 83.14 and 33.41%, respectively. While the effect of PM-CS-dex-NPs was more salient on amastigotes, PM-MCS-dex-NPs effectively affected both stages of the parasite, especially the amastigote one. This indicated that the mannosylated formulation acts as a targeted delivery system. The findings of this study revealed that this novel targeted formulation represented a strong anti-leishmanial activity.
Assuntos
Quitosana , Sistemas de Liberação de Medicamentos , Leishmaniose/tratamento farmacológico , Nanopartículas , Paromomicina/administração & dosagem , Paromomicina/uso terapêutico , Animais , Quitosana/síntese química , Quitosana/química , Nanopartículas/química , Espectroscopia de Infravermelho com Transformada de FourierRESUMO
An extremely sensitive and highly simple aptasensor was fabricated for quantitation of amyloid beta (Aß) by electrochemical transduction of a fern leaves-like gold nanostructure. The gold nanostructure was synthesized by electrodeposition using polyethylene glycol 6000 as a shape-directing agent, and characterized electrochemically and by field emission scanning electron microscopy. A specific RNA aptamer was immobilized on the fern leaves-like gold nanostructure, and binding with Aß was detected by the ferro/ferricyanide redox marker. The designed aptasensor was able to detect Aß in a linear range of 0.002-1.28â¯ngâ¯mL-1 and a limit of detection of 0.4â¯pgâ¯mL-1 (88.6â¯amolâ¯L-1). The aptasensor was interference-free, and for demonstration of its viability for Aß determination in real samples, the human blood serum and artificial cerebrospinal fluid containing Aß were analyzed. The aptasensor is applicable for the assessment and management of Alzheimer's disease at early stages.
Assuntos
Doença de Alzheimer/diagnóstico , Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais , Técnicas Eletroquímicas , Ouro/química , Nanopartículas Metálicas/química , Peptídeos beta-Amiloides/análise , HumanosRESUMO
Capecitabine (CAP) is an FDA-approved and frequently used chemotherapeutic agent for the treatment of various cancers. However, there are some side effects and chemoresistance limiting its use. Nanotechnological approaches can enhance the efficacy of anticancer drugs. In this study, CAP-loaded nanoniosomes were prepared. Nanoniosomes were prepared by the method of thin film hydration wherein CAP was loaded into the nanoniosomes. Nanoniosomes were then characterized by field emission scanning electron microscopy and (particle) vesicle size analysis. The cytotoxicity effect of the nanoniosomes were evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. CAP was loaded into the nanoniosomes and loading capacity and entrapment efficiency were determined. The vesicle size of the nanoniosomes was obtained in the nanometer scale, and CAP release profiles from the nanoniosomes were also obtained. Finally, the cytotoxicity effect of CAP and CAP-loaded nanoniosomes were evaluated toward MCF7 and PANC1 cell lines. The nanoniosomes with an amphipathic structure can penetrate into the cells with an enhanced release rate. These caused the toxicity of drug in the nanoniosomes to be higher than the free drug.
Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Capecitabina/química , Capecitabina/farmacologia , Nanoestruturas/química , Calibragem , Sobrevivência Celular/efeitos dos fármacos , Humanos , Lipossomos , Células MCF-7RESUMO
Prostate Specific Antigen (PSA) is a biomarker employed for detection of prostate cancer. An electrochemical nanobiosensor is designed and fabricated using a molecularly imprinted polymer for the simple and fast PSA detection. The imprinted polymer served as a PSA artificial receptor fabricated by electrochemical polymerization of pyrrole on screen-printed gold electrode in the presence of PSA. PSA was a molecular template for the polymer. The fabricated nanobiosensor was evaluated by differential pulse voltammetry and using K3[Fe(CN)6]/K4[Fe(CN)6] as an electrochemical marker. The factors influencing the performance of the sensor including electropolymerization cycle umbers (to control the thickness of the polymer film) and time of PSA binding were optimized to attain the best sensitivity. The binding affinity of the nanobiosensor surface was examined by the Freundlich isotherm with Freundlich constant and exponent of 0.89â¯ngâ¯mL-1 and 10.93, respectively. The nanobiosensor demonstrated a fast rebinding rate and a high capacity of PSA recognition with detection limit of 2.0â¯pgâ¯mL-1.
Assuntos
Técnicas Biossensoriais/métodos , Técnicas Eletroquímicas/métodos , Calicreínas/sangue , Impressão Molecular/métodos , Antígeno Prostático Específico/sangue , Eletrodos , Ouro/química , Humanos , Limite de Detecção , Masculino , Polímeros/química , Neoplasias da Próstata/metabolismo , Pirróis/químicaRESUMO
A self-nanoemulsifying drug delivery system (SNEDDS) was developed as a novel route to enhance the efficacy of docetaxel lipophilic drug. SNEDDS comprised ethyl oleate, Tween 80 and poly(ethylene glycol) 600, as oil, surfactant and co-surfactant, and formed stabilized monodispersed oil nanodroplets upon dilution in water. SNEDDS represented encapsulation efficiency and loading capacity of 21.4 and 52.7%, respectively. The docetaxel release profile from the drug-loaded SNEDDS was recorded, its effectiveness against MCF-7 cell line was investigated, and an IC50 value of 0.98 ± 0.05 µg mL-1 was attained. The drug-loaded SNEDDS was administrated in rats, and the pharmacokinetic parameters of maximum concentration of 22.2 ± 0.8 µg mL-1, time to attain this maximum concentration of 230 min, and area under the curve of 1.71 ± 0.18 µg min mL-1 were obtained. The developed SNEDDS formulation can be represented as an alternative to docetaxel administration.
Assuntos
Antineoplásicos/administração & dosagem , Sobrevivência Celular/efeitos dos fármacos , Docetaxel/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Emulsificantes/administração & dosagem , Animais , Antineoplásicos/farmacocinética , Sobrevivência Celular/fisiologia , Docetaxel/farmacocinética , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos/métodos , Emulsificantes/farmacocinética , Feminino , Humanos , Células MCF-7 , Ratos , Ratos Sprague-DawleyRESUMO
Detecting and monitoring the pathogens with high selectivity and sensitivity is critical for public health. In the present study, we demonstrated a specific analytical strategy for sensitive detection of Leishmania infantum genome. The developed sensor utilized toluidine blue as a hybridization indicator and a Leishmania infantum-specific capture DNA sequence immobilized on a high-surface area gold nanostructure as an electrochemical transducer. The produced analytical response was based on the hybridization of the single-stranded DNA from the target with the immobilized DNA sequence at the electrode surface. The developed DNA sensor in this study was successfully employed to detect a synthetic Leishmania infantum target sequence in a wide concentration range from 1â¯×â¯10-18 to 1â¯×â¯10-10â¯molâ¯L-1 with a detection limit of 0.2â¯amolâ¯L-1 with the ability to discriminate the target sequence from mismatched sequences. Moreover, the designed DNA sensor showed a good reproducibility and stability during repeated regeneration and hybridization cycles. The DNA sensor could detect Leishmania infantum genome in a wide concentration range from 15 to 50â¯ng⯵L-1 with a detection limit of 29â¯ng⯵L-1. Furthermore, clinical trials confirmed the applicability of the developed DNA sensor for practical applications.
Assuntos
DNA Bacteriano/análise , Técnicas Eletroquímicas , Ouro/química , Leishmania infantum/isolamento & purificação , Nanopartículas Metálicas/química , DNA Bacteriano/metabolismo , DNA de Cadeia Simples/química , DNA de Cadeia Simples/metabolismo , Eletrodos , Genoma Bacteriano , Ácidos Nucleicos Imobilizados/química , Ácidos Nucleicos Imobilizados/metabolismo , Leishmania infantum/genética , Limite de Detecção , Hibridização de Ácido Nucleico , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Acute myocardial infarction (MI) accounts for one third of deaths. Cardiac troponin I (TnI) is a reliable biomarker of cardiac muscle tissue injury and is employed in the early diagnosis of MI. OBJECTIVE: In this study, a molecular method is introduced to early diagnosis of MI by rapid detection of TnI. MATERIALS AND METHODS: The detection method was based on electrochemical aptasensing, being developed using different methods and evaluation steps. A gold electrode was used as a transducer to successful immobilize 76base aptamer to fabricate a TnI biosensor. RESULTS: The designed aptasensor could detect TnI in a range of 0.03 to 2.0 ng mL-1 without using any label, pre-concentration or amplification steps. The limit of detection was attained as 10 pg mL-1 without significant trouble of interfering species. The TnI biosensor demonestrated a stable, regenerative and reproducible function. 89 human samples were used to evaluate the performance of the TnI biosensor, and it represented 100% and 81%, diagnostic sensitivity and specificity, respectively. CONCLUSION: This aptasensor may be used as an applicable tool in the future of early medical diagnosis of MI.
RESUMO
Leishmaniasis is a group of parasitic disease caused by protozoa of Leishmania genus. Leishmania major accounts for the cutaneous leishmaniasis (CL). The current treatments of this disease are expensive with high toxicity and are associated to difficulties of healing and parasite resistance. Miltefosine and ketoconazole have been found to be effective against CL. In this study, miltefosine- and ketoconazole-loaded nanoniosomes were prepared by the thin film-hydration method, and their anti-leishmanial effects against Leishmania major promastigotes and amastigotes were evaluated. The particle size and zeta potential of the nanoniosomes were determined. Release from the formulations showed enhanced and controlled dissolution of the drugs. The miltefosine- and ketoconazole-loaded nanoniosomes inhibited the growth of promastigote and amastigote forms of Leishmania major in vitro after 48â¯h of incubation and had IC50 values of 53.39⯱â¯0.02 and 86.38⯱â¯0.07⯵gâ¯mL-1, respectively. The formulations provided improved anti-leishmanial activities for the treatment of cutaneous leishmaniasis.
Assuntos
Antiprotozoários/uso terapêutico , Cetoconazol/uso terapêutico , Leishmania major/efeitos dos fármacos , Leishmaniose Cutânea/tratamento farmacológico , Nanoestruturas , Fosforilcolina/análogos & derivados , Animais , Antiprotozoários/farmacologia , Cetoconazol/farmacologia , Fosforilcolina/farmacologia , Fosforilcolina/uso terapêuticoRESUMO
Bacteria, parasites and viruses are found widely in the environment as potential pathogens, and can be the source of infections. Therefore, sensitive and rapid methods for identification of the pathogens are required to achieve a better quality of life. Enterococcus faecalis commonly colonizes and threatens human health. In the present study, we demonstrate the fabrication of a novel electrochemical DNA biosensor based on electrodeposited gold nanostructures as a transducer substrate combined with toluidine blue (TB) as a redox marker. Binding of TB with the single and double stranded DNA (ssDNA and dsDNA) was shortly investigated, and based on the results, TB could discriminate between ssDNA and dsDNA. A specific thiolated ssDNA sequence was immobilized on the transducer substrate, and DNA hybridization was followed by differential pulse voltammetry. The DNA biosensor showed excellent performances with high sensitivity and good selectivity. The DNA biosensor was applied to detect a synthetic target in a linear range of 1.0â¯×â¯10-17-1.0â¯×â¯10-10â¯molâ¯L-1 with a limit of detection (LOD) of 4.7â¯×â¯10-20â¯molâ¯L-1. In addition, LOD of the DNA biosensor for the detection of genomic DNA was found to be 30.1â¯ng µL-1.
Assuntos
Técnicas Biossensoriais/métodos , DNA/química , Técnicas Eletroquímicas/métodos , Enterococcus faecalis/genética , Ouro/química , Nanopartículas Metálicas/química , Enterococcus faecalis/isolamento & purificaçãoRESUMO
Hierarchical leaf-like gold nanolayers were electrodeposited using choline chloride as a shape directing agent and characterized using field emission scanning electron microscopy. The electrooxidation behavior of vorinostat was then studied on the nanolayers and the kinetic parameters of the electrodic process were obtained by voltammetric measurements in a phosphate buffer solution at pH 7.40. Vorinostat was electrooxidized on the nanolayers' surface at a lower potential and with a higher rate, compared to a polycrystalline smooth gold surface, through an irreversible process. Based on the results, an amperometric sensor was designed using the hierarchical leaf-like gold nanolayers for the determination of vorinostat. A linear dynamic range of 4.0-52µmol L-1 with a calibration sensitivity of 7.7mAmol-1L, and a detection limit of 1.40µmolL-1 were obtained. The amperometry method was also applied to the analysis of vorinostat capsules.
Assuntos
Eletroquímica/métodos , Ouro/química , Ácidos Hidroxâmicos/análise , Nanoestruturas/química , Colina/química , Eletroquímica/instrumentação , Eletrodos , Galvanoplastia , Ácidos Hidroxâmicos/química , Limite de Detecção , Oxirredução , VorinostatRESUMO
Breast cancer is the top cancer and a main cause of death among women. The incidence of this cancer is increasing in the world. Sunitinib maleate is an oral, small-molecule, multi-targeted receptor tyrosine kinase inhibitor that inhibits tumor cell proliferation and angiogenesis, and has been administrated as an anticancer drug. Self-nanoemulsifying drug delivery system (SNEDDS) is an isotopic mixture of an oil, a surfactant and usually a co-surfactant, which can spontaneously form fine oil-in-water nanoemulsion in aqueous media. Here, a SNEDDS composed of 15% ethyl oleate (as an oil phase), 30% tween 80 (as a surfactant), and 55% PEG 600 (as a co-surfactant) was prepared and developed as a carrier for sunitinib. The average droplet size of sunitinib-loaded SNEDDS was 29.5±6.3nm with a stability of more than one month. Sunitinib release from SNEDDS was enhanced accompanied by a controlled dissolution of the drug. Cytotoxicity studies on 4T1 and MCF-7 cell lines indicated a toxicity enhancement in sunitinib by SNEDDS. To inspect the bioavailability of the drug-loaded SNEDDS after oral administration with a dose of 50mgkg-1, the maximum plasma concentration and the mean area under the plasma concentration-time curve were measured. It was found that these parameters were increased 1.45- and 1.24-times respectively, compared to a drug suspension.
Assuntos
Sistemas de Liberação de Medicamentos/métodos , Emulsões/química , Indóis/administração & dosagem , Nanopartículas/química , Pirróis/administração & dosagem , Animais , Antineoplásicos/administração & dosagem , Antineoplásicos/química , Antineoplásicos/farmacocinética , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Humanos , Indóis/química , Indóis/farmacocinética , Células MCF-7 , Masculino , Camundongos , Tamanho da Partícula , Pirróis/química , Pirróis/farmacocinética , Ratos Sprague-Dawley , Sunitinibe , Distribuição TecidualRESUMO
Erlotinib was loaded on albumin nanoparticles for the first time and the cytotoxic effect of the resulting nanoparticles against ASPC-1 and PANC-1 pancreatic adenocarcinoma cell lines was evaluated. The carrier (albumin nanoparticles, ANPs) was synthesized by desolvation method using a mixed solvent followed by thermal crosslinking for stabilization. ANPs and the drug-loaded ANPs were characterized by field emission scanning and transmission electron microscopies, particle size analysis and Fourier transform infrared spectroscopy. The nanoformulation had a size of <14nm with a good monodispersity. Drug loading and encapsulation efficiencies were evaluated as 27 and 44%. Cytotoxicity assays after 72h revealed the potential of ANPs to improve erlotinib toxicity (54% against 34% of free drug toward ASPC-1 cell line, and 52% against 30% toward PANC-1 cell line). Values of IC50 were obtained for both cell lines and indicated significant reduction in the erlotinib dose necessary for killing the cells, while, ANPs were completely safe. The results demonstrated that erlotinib-loaded ANPs had a remarkable potential for pancreatic cancer drug delivery.