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1.
Arch Microbiol ; 206(4): 134, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38433145

RESUMO

Acanthamoeba castellanii are opportunistic pathogens known to cause infection of the central nervous system termed: granulomatous amoebic encephalitis, that mostly effects immunocompromised individuals, and a sight threatening keratitis, known as Acanthamoeba keratitis, which mostly affects contact lens wearers. The current treatment available is problematic, and is toxic. Herein, an amphiphilic star polymer with AB2 miktoarms [A = hydrophobic poly(ℇ-Caprolacton) and B = hydrophilic poly (ethylene glycol)] was synthesized by ring opening polymerization and CuI catalyzed azide-alkyne cycloaddition. Characterization by 1H and 13C NMR spectroscopy, size-exclusion chromatography and fluorescence spectroscopy was accomplished. The hydrophobic drug itraconazole (ITZ) was incorporated in self-assembled micellar structure of AB2 miktoarms through co-solvent evaporation. The properties of ITZ loaded (ITZ-PCL-PEG2) and blank micelles (PCL-PEG2) were investigated through zeta sizer, scanning electron microscopy and Fourier-transform infrared spectroscopy. Itraconazole alone (ITZ), polymer (DPB-PCL), empty polymeric micelles (PCL-PEG2) alone, and itraconazole loaded in polymeric micelles (ITZ-PCL-PEG2) were tested for anti-amoebic potential against Acanthamoeba, and the cytotoxicity on human cells were determined. The polymer was able to self-assemble in aqueous conditions and exhibited low value for critical micelle concentration (CMC) 0.05-0.06 µg/mL. The maximum entrapment efficiency of ITZ was 68%. Of note, ITZ, DPB, PCL-PEG2 and ITZ-PCL-PEG2 inhibited amoebae trophozoites by 37.34%, 36.30%, 35.77%, and 68.24%, respectively, as compared to controls. Moreover, ITZ-PCL-PEG2 revealed limited cytotoxicity against human keratinocyte cells. These results are indicative that ITZ-PCL-PEG2 micelle show significantly better anti-amoebic effects as compared to ITZ alone and thus should be investigated further in vivo to determine its clinical potential.


Assuntos
Acanthamoeba castellanii , Micelas , Humanos , Itraconazol/farmacologia , Alcinos , Polímeros
2.
Biometals ; 37(1): 171-184, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-37792257

RESUMO

The development of antibiotic alternatives that entail distinctive chemistry and modes of action is necessary due to the threat posed by drug resistance. Nanotechnology has gained increasing attention in recent years, as a vehicle to enhance the efficacy of existing antimicrobials. In this study, Chitosan copper oxide nanoparticles (CHI-CuO) were synthesized and were further loaded with Quercetagetin (QTG) to achieve the desired (CHI-CuO-QTG). Size distribution, zeta potential and morphological analysis were accomplished. Next, the developed CHI-CuO-QTG was assessed for synergistic antibacterial properties, as well as cytotoxic attributes. Bactericidal assays revealed that CHI-CuO conjugation showed remarkable effects and enhanced QTG effects against a range of Gram + ve and Gram - ve bacteria. The MIC50 of QTG against S. pyogenes was 107 µg/mL while CHI-CuO-QTG reduced it to 9 µg/mL. Similar results were observed when tested against S. pneumoniae. Likewise, the MIC50 of QTG against S. enterica was 38 µg/mL while CHI-CuO-QTG reduced it to 7 µg/mL. For E. coli K1, the MIC50 of QTG was 42 µg/mL while with CHI-CuO-QTG it was 23 µg/mL. Finally, the MIC50 of QTG against S. marcescens was 98 µg/mL while CHI-CuO-QTG reduced it to 10 µg/mL. Notably, the CHI-CuO-QTG nano-formulation showed limited damage when tested against human cells using lactate dehydrogenase release assays. Importantly, bacterial-mediated human cell damage was reduced by prior treatment of bacteria using drug nano-formulations. These findings are remarkable and clearly demonstrate that drug-nanoparticle formulations using nanotechnology is an important avenue in developing potential therapeutic interventions against microbial infections.


Assuntos
Quitosana , Flavonas , Nanopartículas Metálicas , Nanopartículas , Humanos , Quitosana/farmacologia , Quitosana/química , Cobre/farmacologia , Cobre/química , Escherichia coli , Antibacterianos/farmacologia , Antibacterianos/química , Bactérias , Óxidos , Nanopartículas Metálicas/química , Testes de Sensibilidade Microbiana
3.
Biometals ; 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38705945

RESUMO

With the emergence of drug-resistance, there is a need for novel anti-bacterials or to enhance the efficacy of existing drugs. In this study, Patuletin (PA), a flavanoid was loaded onto Gallic acid modified Zinc oxide nanoparticles (PA-GA-ZnO), and evaluated for antibacterial properties against Gram-positive (Bacillus cereus and Streptococcus pneumoniae) and Gram-negative (Samonella enterica and Escherichia coli) bacteria. Characterization of PA, GA-ZnO and PA-GA-ZnO' nanoparticles was accomplished utilizing fourier-transform infrared spectroscopy, efficiency of drug entrapment, polydispersity index, zeta potential, size, and surface morphology analysis through atomic force microscopy. Using bactericidal assays, the results revealed that ZnO conjugation displayed remarkable effects and enhanced Patuletin's effects against both Gram-positive and Gram-negative bacteria, with the minimum inhibitory concentration observed at micromolar concentrations. Cytopathogenicity assays exhibited that the drug-nanoconjugates reduced bacterial-mediated human cell death with minimal side effects to human cells. When tested alone, drug-nanoconjugates tested in this study showed limited toxic effects against human cells in vitro. These are promising findings, but future work is needed to understand the molecular mechanisms of effects of drug-nanoconjugates against bacterial pathogens, in addition to in vivo testing to determine their translational value. This study suggests that Patuletin-loaded nano-formulation (PA-GA-ZnO) may be implicated in a multi-target mechanism that affects both Gram-positive and Gram-negative pathogen cell structures, however this needs to be ascertained in future work.

4.
Arch Microbiol ; 205(5): 170, 2023 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-37017767

RESUMO

Balamuthia mandrillaris and Naegleria fowleri are protist pathogens that can cause fatal infections. Despite mortality rate of > 90%, there is no effective therapy. Treatment remains problematic involving repurposed drugs, e.g., azoles, amphotericin B and miltefosine but requires early diagnosis. In addition to drug discovery, modifying existing drugs using nanotechnology offers promise in the development of therapeutic interventions against these parasitic infections. Herein, various drugs conjugated with nanoparticles were developed and evaluated for their antiprotozoal activities. Characterizations of the drugs' formulations were accomplished utilizing Fourier-transform infrared spectroscopy, efficiency of drug entrapment, polydispersity index, zeta potential, size, and surface morphology. The nanoconjugates were tested against human cells to determine their toxicity in vitro. The majority of drug nanoconjugates exhibited amoebicidal effects against B. mandrillaris and N. fowleri. Amphotericin B-, Sulfamethoxazole-, Metronidazole-based nanoconjugates are of interest since they exhibited significant amoebicidal effects against both parasites (p < 0.05). Furthermore, Sulfamethoxazole and Naproxen significantly diminished host cell death caused by B. mandrillaris by up to 70% (p < 0.05), while Amphotericin B-, Sulfamethoxazole-, Metronidazole-based drug nanoconjugates showed the highest reduction in host cell death caused by N. fowleri by up to 80%. When tested alone, all of the drug nanoconjugates tested in this study showed limited toxic effects against human cells in vitro (less than 20%). Although these are promising findings, prospective work is warranted to comprehend the mechanistic details of nanoconjugates versus amoebae as well as their in vivo testing, to develop antimicrobials against the devastating infections caused by these parasites.


Assuntos
Amebíase , Amebicidas , Balamuthia mandrillaris , Naegleria fowleri , Humanos , Anfotericina B/farmacologia , Metronidazol/farmacologia , Metronidazol/uso terapêutico , Nanoconjugados/química , Nanoconjugados/uso terapêutico , Estudos Prospectivos , Amebicidas/química , Amebicidas/farmacologia , Sulfametoxazol/farmacologia , Sulfametoxazol/uso terapêutico , Amebíase/tratamento farmacológico , Amebíase/parasitologia
5.
J Appl Microbiol ; 134(4)2023 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-37024269

RESUMO

AIM: Herein, the anti-parasitic activity of azoles (fluconazole and itraconazole) and 5-nitroimdazole (metronidazole) against the brain-eating amoebae: Naegleria fowleri and Balamuthia mandrillaris was elucidated. METHODS AND RESULTS: Azoles and 5-nitroimidazole based nanoformulations were synthesized and characterized using a UV-visible spectrophotometer, atomic force microscopy, and fourier transform infrared spectroscopy. H1-NMR, EI-MS, and ESI-MS were performed to determine their molecular mass and elucidate their structures. Their size, zeta potential, size distribution, and polydispersity index (PDI) were assessed. Amoebicidal assays revealed that all the drugs and their nanoformulations, (except itraconazole) presented significant anti-amoebic effects against B. mandrillaris, while all the treatments indicated notable amoebicidal properties against N. fowleri. Amoebicidal effects were radically enhanced upon conjugating the drugs with nanoparticles. The IC50 values for KM-38-AgNPs-F, KM-20-AgNPs-M, and KM-IF were 65.09, 91.27, and 72.19 µg.mL-1, respectively, against B. mandrillaris. Whereas against N. fowleri, the IC50 values were: 71.85, 73.95, and 63.01 µg.mL-1, respectively. Additionally, nanoformulations significantly reduced N. fowleri-mediated host cell death, while nanoformulations along with fluconazole and metronidazole considerably reduced Balamuthia-mediated human cell damage. Finally, all the tested drugs and their nanoformulations revealed limited cytotoxic activity against human cerebral microvascular endothelial cell (HBEC-5i) cells. CONCLUSION: These compounds should be developed into novel chemotherapeutic options for use against these distressing infections due to free-living amoebae, as currently there are no effective treatments.


Assuntos
Amebicidas , Amoeba , Antiprotozoários , Naegleria fowleri , Humanos , Azóis/farmacologia , Fluconazol/farmacologia , Metronidazol/farmacologia , Itraconazol/farmacologia , Antiprotozoários/farmacologia , Amebicidas/farmacologia , Amebicidas/química , Encéfalo
6.
Exp Parasitol ; 246: 108474, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36708943

RESUMO

Acanthamoeba castellanii causes granulomatous amoebic encephalitis, an uncommon but severe brain infection and sight-threatening Acanthamoeba keratitis. Most of the currently used anti-amoebic treatments are not always effective, due to persistence of the cyst stage, and recurrence can occur. Here in this study we synthesize cinnamic acid and lactobionic acid-based magnetic nanoparticles (MNPs) using co-precipitation technique. These nanoformulations were characterized by Fourier transform infrared spectroscopy and Atomic form microscopy. The drugs alone (Hesperidin, Curcumin and Amphotericin B), magnetic NPs alone, and drug-loaded nano-formulations were evaluated at a concentration of 100 µg/mL for antiamoebic activity against a clinical isolate of A. castellanii. Amoebicidal assays revealed that drugs and conjugation of drugs and NPs further enhanced amoebicidal effects of drug-loaded nanoformulations. Drugs and drug-loaded nanoformulations inhibited both encystation and excystation of amoebae. In addition, drugs and drug-loaded nanoformulations inhibited parasite binding capability to the host cells. Neither drugs nor drug-loaded nanoformulations showed cytotoxic effects against host cells and considerably reduced parasite-mediated host cell death. Overall, these findings imply that conjugation of medically approved drugs with MNPs produce potent anti-Acanthamoebic effects, which could eventually lead to the development of therapeutic medications.


Assuntos
Acanthamoeba castellanii , Amebíase , Amebicidas , Nanopartículas Metálicas , Humanos , Nanopartículas Metálicas/química , Amebíase/parasitologia , Amebicidas/química
7.
Pak J Med Sci ; 39(6): 1647-1651, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37936786

RESUMO

Objective: To investigate the Bioequivalence of Anplag® 90mg (Ticagrelor) tablet and Brilinta® 90 mg (Ticagrelor) tablet under fasting conditions in healthy Pakistani subjects. Method: This was an open-label, cross-over, randomized, single-dose, two-period, single-center Bioequivalence Study conducted at Center of Bioequivalence Studies and Clinical Research (CBSCR), ICCBS, University of Karachi, Karachi, Pakistan from September 2020 to January 2021. This was an open-label, randomized, single-dose, two-period, cross-over Bioequivalence Study. After randomization, a single dose of Ticagrelor 90mg tablet (test or reference drug) were administered orally in 1:1 ratio to each subject under fasting conditions. Seven days washout period was kept between the two periods in order to avoid carry over. Blood samples were then taken up to 48th hours post-dose. Point estimates and 90% confidence intervals (CI) for the ratio of the log-transformed values were calculated. Bioequivalence assessment of both, the reference and the test drugs were based on the primary Pharmacokinetic PK metrics including peak maximum concentration (Cmax), area under the curve (AUC) from zero to last quantifiable concentration (AUClast), and AUC from zero to infinity (AUCtotal) after log-transformation of data with ANOVA. In this bioequivalence study, the primary pharmacokinetic parameters were assessed for both Ticagrelor and its Active Metabolite (AR-C124910XX). Safety endpoints were evaluated by monitoring adverse events (AEs). Results: The 90% Confidence Intervals (CIs) of the Geometric Mean Ratio for primary PK parameters including Cmax, AUClast, and AUCtotal all were within the accepted bioequivalence range of 80%- 125%. In the current study, no serious adverse events were reported. Conclusion: Our results showed that the two tested formulations of Ticagrelor tablets were bioequivalent and well tolerated.Trial Registration: ClinicalTrials.gov Identifier: NCT04941196.

8.
J Biol Inorg Chem ; 27(4-5): 471-483, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35821138

RESUMO

A sensitive scheme was established for the detection of vitamin C (Ascorbic acid) and vitamin B1 (Thiamin HCl) using Maltol capped AgNPs (McAgNPs) as colorimetric sensor. The designed scheme showed an instant alteration in color from yellow to orange and green for vitamin-C and vitamin B1 sequentially. The probe was sensitive in a concentration range of (0-1 µM) with limit of detection 0.064 and 0.038 µM for vitamin C and vitamin B1 sequentially. The interaction mechanism between vitamin C and vitamin B1 and McAgNPs was evaluated by visible spectroscopy, FTIR, and AFM. Vitamin C attaches on the surface of nanoparticles by C=O group, while OH, C-S-C, and NH2 groups are involved in the binding of vitamin B1 with McAgNPs. The Vit-C/Vit-B1-McAgNPs complexes were stable over a wide range of pHs. The size of McAgNPs increased after the interaction of vitamin C/vitamin B1 from 30-40 nm to 500 and 400 nm sequentially. The scheme was successfully applied for the detection of vitamin C and vitamin B1 in urine, plasma, water, and commercial pharmaceutical tablets with good recoveries. The scheme was ascertained to be more sensitive than many other formerly described schemes.


Assuntos
Colorimetria , Nanopartículas Metálicas , Ácido Ascórbico , Colorimetria/métodos , Aromatizantes , Nanopartículas Metálicas/química , Prata/química , Tiamina , Vitaminas
9.
Molecules ; 27(19)2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36235305

RESUMO

Hydrazones are active compounds having an azomethine -NHN=CH group and are widely studied owing to their ease of preparation and diverse pharmacological benefits. Novel isonicotinic hydrazone derivatives of vanillin aldehyde and salicyl aldehyde were synthesized that had azomethine linkages and were characterized by UV-Visible, FTIR, EI-MS, 1H-NMR and 13C-NMR spectroscopy. The compounds were screened for their antibacterial activity against Staphylococcus aureus, Bacillus subtilus, and Escherichia coli using disc diffusion and minimum inhibitory concentration (MIC) methods. For cytotoxicity, a brine shrimp lethality test was performed to calculate the lethal concentration (LC50). The results demonstrated appreciable antibacterial activities against the applied strains, amongst which the compounds coded NH3 and NH5 showed maximum inhibition and MIC responses. In terms of cytotoxic activity, the maximum effect was observed in compound NH5 and NH6 treatments with minimum survival percentages of 36.10 ± 3.45 and 32.44 ± 2.0, respectively. These hydrazones could be potential candidates in antitumorigenic therapy against various human cancer cells.


Assuntos
Antineoplásicos , Hidrazonas , Aldeídos/farmacologia , Antibacterianos/química , Antineoplásicos/farmacologia , Compostos Azo , Escherichia coli , Humanos , Hidrazonas/química , Testes de Sensibilidade Microbiana , Tiossemicarbazonas
10.
BMC Microbiol ; 21(1): 51, 2021 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-33596837

RESUMO

BACKGROUNDS: Escherichia coli K1 causes neonatal meningitis. Transcriptome studies are indispensable to comprehend the pathology and biology of these bacteria. Recently, we showed that nanoparticles loaded with Hesperidin are potential novel antibacterial agents against E. coli K1. Here, bacteria were treated with and without Hesperidin conjugated with silver nanoparticles, and silver alone, and 50% minimum inhibitory concentration was determined. Differential gene expression analysis using RNA-seq, was performed using Degust software and a set of genes involved in cell stress response and metabolism were selected for the study. RESULTS: 50% minimum inhibitory concentration with silver-conjugated Hesperidin was achieved with 0.5 µg/ml of Hesperidin conjugated with silver nanoparticles at 1 h. Differential genetic analysis revealed the expression of 122 genes (≥ 2-log FC, P< 0.01) in both E. coli K1 treated with Hesperidin conjugated silver nanoparticles and E. coli K1 treated with silver alone, compared to untreated E. coli K1. Of note, the expression levels of cation efflux genes (cusA and copA) and translocation of ions, across the membrane genes (rsxB) were found to increase 2.6, 3.1, and 3.3- log FC, respectively. Significant regulation was observed for metabolic genes and several genes involved in the coordination of flagella. CONCLUSIONS: The antibacterial mechanism of nanoparticles maybe due to disruption of the cell membrane, oxidative stress, and metabolism in E. coli K1. Further studies will lead to a better understanding of the genetic mechanisms underlying treatment with nanoparticles and identification of much needed novel antimicrobial drug candidates.


Assuntos
Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Escherichia coli/genética , Perfilação da Expressão Gênica , Hesperidina/farmacologia , Nanopartículas Metálicas/química , Prata/farmacologia , Hesperidina/química , Testes de Sensibilidade Microbiana , Estresse Oxidativo/efeitos dos fármacos , Transcriptoma
11.
Biotechnol Appl Biochem ; 68(5): 992-1002, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32885506

RESUMO

This study reports the green synthesis and urease inhibitory activities of Ag and Au nanoparticles (NPs) using Crataegus oxyacantha extract. The synthesized NPs were characterized by UV-visible, FT-IR spectroscopy, atomic force microscopy, and scanning electron microscopy. The obtained NPs were spherical in shape, and their size was around 85 nm. A strong correlation between the phytochemicals present in the extract and their capability for the synthesis of NPs was observed. Furthermore, the shape, size, stability, and bioactivity of the NPs were strongly influenced by the stabilizing phytochemicals. The experimental analysis suggested that these NPs have substantial stability in a diverse range of physiological conditions such as pH, salinity, and temperature. The NPs exhibited potent urease enzyme inhibitory activities with percent inhibition of 99.25 and IC50 value of 1.38 ± 0.3, comparable to the standard (thiourea percent inhibition, that is, 98.2% and IC50 value 5.3 ± 0.04). These results suggested that the proposed NPs could be used in the homeopathic and pharmaceutical industries for biomedical applications.


Assuntos
Crataegus/química , Inibidores Enzimáticos/farmacologia , Química Verde , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Urease/antagonistas & inibidores , Canavalia/enzimologia , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Ouro/química , Ouro/farmacologia , Nanopartículas Metálicas/química , Tamanho da Partícula , Compostos Fitoquímicos/química , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/química , Extratos Vegetais/isolamento & purificação , Prata/química , Prata/farmacologia , Urease/metabolismo
12.
Sensors (Basel) ; 21(21)2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34770608

RESUMO

Highly stable, small-sized and evenly distributed solid mercury nanoparticles capped with ibuprofen (Ibu-HgNPs) were prepared via reduction with hydrazine and capped with ibuprofen as a stabilizing agent. Characterization of Ibu-HgNPs was carried out by UV-Vis spectrophotometry and transmission electron microscopy (TEM). The prepared Ibu-HgNPs were immobilized onto a glassy carbon electrode (GCE) and used for the first time as the sensing element for voltammetric determination of low concentrations of acrylamide (AA) in aqueous solutions. Various parameters such as the type of supporting electrolyte, voltammetric mode, frequency, deposition time, stirring rate and initial potential were optimized to obtain the highest peak current of AA. The sensor delivered the best results in combination with the square wave voltammetry (SWV) mode, with good repeatability (relative standard deviation (RSD) of 25 repetitions was 1.4% for 1000 ppb AA). The study further revealed that Ibu-HgNPs are strongly adhered to GCE and hence do not contaminate the environment even after several runs. The newly developed AA sensor provides linear calibration dependence in the range of 100-1300 ppb with an R2 value of 0.996 and limit of detection (LOD) of 8.5 ppb. Negligible interference was confirmed from several organic compounds, cations and anions. The developed sensor was successfully applied for AA determination in various types of environmental real water samples to prove its practical usefulness and applicability.


Assuntos
Mercúrio , Nanopartículas , Acrilamida , Técnicas Eletroquímicas , Eletrodos , Ibuprofeno
13.
Pharm Dev Technol ; 26(3): 291-301, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33475034

RESUMO

The current study focuses on the development, characterization, biocompatibility investigation and oral bioavailability evaluation of ceftriaxone (CFT)-loaded lactobionic acid (LBA)-functionalized iron oxide magnetic nanoparticles (MNP-LBA). Atomic force microscopy and dynamic light scattering showed that the developed CFT-loaded MNP-LBA is spherical, with a measured hydrodynamic size of 147 ± 15.9 nm and negative zeta potential values (-35 ± 0.58 mV). Fourier transformed infrared analysis revealed interactions between the nanocarrier and the drug. Nanoparticles showed high drug entrapment efficiencies of 91.5 ± 2.2%, and the drug was released gradually in vitro and shows prolonged in vitro stability using simulated gastrointestinal (GI) fluids. The formulations were found to be highly biocompatible (up to 100 µg/mL) and hemocompatible (up to 1.0 mg/mL). Using an albino rabbit model, the formulation showed a significant enhancement in drug plasma concentration up to 14.46 ± 2.5 µg/mL in comparison with its control (1.96 ± 0.58 µg/mL). Overall, the developed MNP-LBA formulation was found promising for provision of high-drug entrapment, gradual drug release and was appropriate for enhancing the oral delivery of CFT.


Assuntos
Antibacterianos/administração & dosagem , Ceftriaxona/administração & dosagem , Dissacarídeos/química , Portadores de Fármacos/química , Nanopartículas Magnéticas de Óxido de Ferro/química , Administração Oral , Animais , Antibacterianos/sangue , Disponibilidade Biológica , Ceftriaxona/sangue , Coelhos
14.
Angew Chem Int Ed Engl ; 60(36): 19614-19619, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34263514

RESUMO

Fluorescent chemosensors are powerful imaging tools in the fields of life sciences and engineering. Based on the principle of supramolecular chemistry, indicator displacement assay (IDA) provides an alternative approach for constructing and optimizing chemosensors, which has the advantages of simplicity, tunability, and modularity. However, the application of IDA in bioimaging continues to face a series of challenges, including interfering signals, background noise, and inconsistent spatial location. Accordingly, we herein report a supramolecular bioimaging strategy of Förster resonance energy transfer (FRET)-assisted IDA by employing macrocyclic amphiphiles as the operating platform. By merging FRET with IDA, the limitations of IDA in bioimaging were addressed. As a proof of concept, the study achieved mitochondria-targeted imaging of adenosine triphosphate in live cells with signal amplification. This study opens a non-covalent avenue for bioimaging with advancements in tunability, generality, and simplicity, apart from the covalent approach.


Assuntos
Transferência Ressonante de Energia de Fluorescência , Corantes Fluorescentes/química , Indicadores e Reagentes/química , Células Hep G2 , Humanos , Substâncias Macromoleculares/análise , Espectrometria de Fluorescência
15.
Bioorg Chem ; 100: 103937, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32460178

RESUMO

In treating wounds, long lasting infection is considered the major impediment. Drugs are rendered ineffective by pathogenic microorganisms via antibiotic resistance and calls for designing and development of new drugs. Herein, we report synthesis of eight different N-alkylated pyridine-based organic salts QAS 1-8 and their antibacterial, antibiofilm and wound healing activities. 3-(2-R-hydrazinecarbonyl)-1-propylpyridinium Bromide was the parent compound while R group was varying in each salt composed of different aromatic aldehyde moieties. In the antibacterial activity against S. aureus and E. coli, amoxicillin shows IC50 near to 25 µg/mL inhibiting 58 ± 0.4% S. aureus while ceftriaxone inhibited 55 ± 0.5% E. coli at a concentration of 10 µg/mL. The highest IC50 (56 ± 0.5% against S. aureus; 55 ± 0.5% against E. coli) was shown by compound QAS 7 at the concentration of 100 µg/mL; followed by the QAS 6 (55 ± 0.5% against E. coli) and QAS 2 (55 ± 0.5% against E. coli). In the antibiofilm activity, QAS 6, QAS 1 and QAS 8 inhibited 58 ± 0.4% S. aureus at a concentration of 75 µg/mL, while QAS 2 inhibited E. coli at the same concentration and amount. QAS 7, 3 and 1 inhibited almost 90% while QAS 6 inhibited 95 ± 1.1%of E. coli at a concentration of 250 µg/mL. Highest MBIC was provided by QAS 7 (52 ± 0.4%) against S. aureus at a concentration of 50 µg/mL that is very near to the standard amoxicillin. Antibacterial and antibiofilm activity results were also supported by the atomic force microscopy (AFM). In the wound healing activity, QAS 8 healed 90.8 ± 4.3% of the wound in 21 days with an average period of epithelialization (POE) of 19 ± 1.4 days; that is far better than povidone iodine ointment (81.5 ± 3.3% of the wound in the 21 days with 22.4 ± 2.9 days of POE). It is concluded from this study that the synthesized compounds QAS 2, 7 and 8 can be used for further mechanistic studies to be employed as antibacterial, antibiofilm and wound healing agents.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Piridinas/química , Cicatrização/efeitos dos fármacos , Animais , Antibacterianos/síntese química , Antibacterianos/química , Escherichia coli/efeitos dos fármacos , Escherichia coli/fisiologia , Camundongos , Testes de Sensibilidade Microbiana , Microscopia de Força Atômica , Piridinas/síntese química , Piridinas/farmacologia , Sais/química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Relação Estrutura-Atividade
16.
J Liposome Res ; 30(3): 255-262, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31185766

RESUMO

Nonionic surfactants have an extraordinary fascination for the researchers in the field of drug delivery for enhancing drug bioavailability and therapeutic efficacy. Here, we are reporting the synthesis, characterization, drug entrapment efficiency (EE), critical micellar concentration, and biocompatibility evaluation of sulphanilamide based new nonionic surfactants. The surfactants were synthesized in single step reactions and characterized through 1H NMR, FT-IR, and mass spectrometric analysis. The surfactants abilities for niosomal vesicles formation were investigated utilizing Ciprofloxacin as a model drug. The drug loaded niosomal suspension of the synthesized surfactants was screened for shape; size, polydispersity index, and drug EE utilizing AFM, Zetasizer, and UV, respectively. The compatibility of the drug in drug loaded vesicles with excipients was assessed utilizing FT-IR spectroscopy. The biocompatibility of the synthesized surfactants was assessed through blood haemolysis and cell cytotoxicity assays. Results of this study showed that the synthesized surfactants were quite haemocompatible and nontoxic in nature and were able to form spherical vesicles. The size and drug EE of the vesicles were dependant on the length of surfactant aliphatic chain. Surfactant with long aliphatic chain was more efficient in entrapping the drug and could be used as a potential vesicular drug delivery vehicle for improving the lipophilic drug's bioavailability.


Assuntos
Hemólise/efeitos dos fármacos , Sulfanilamida/farmacologia , Tensoativos/síntese química , Tensoativos/farmacologia , Animais , Disponibilidade Biológica , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Camundongos , Estrutura Molecular , Células NIH 3T3 , Tamanho da Partícula , Sulfanilamida/síntese química , Sulfanilamida/química , Propriedades de Superfície , Tensoativos/química
17.
Waste Manag Res ; 38(11): 1269-1277, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32077381

RESUMO

The present work is focused on pyrolysis of polystyrene waste for production of combustible hydrocarbons. The experiments were performed in an indigenously made furnace in the presence of a laboratory synthesised copper oxide. The pyrolysis products were collected and characterised. The Fourier transform infrared spectra showed that the liquid fraction contains C-H, C-O, C-C, C=C and O-H bonds, which correspond to various aliphatic and aromatic compounds. Gas chromatography-mass spectrometry traced compounds ranging from C1 to C4 in the gaseous fraction, whereas in the liquid fraction 15 components ranging from C3 to C24 were detected. From the results it has been concluded that CuO as a catalyst not only increased the liquid yield but also reduced the degradation temperature to great extent. Fuel properties of the pyrolysis oil were determined and compared with standard values of commercial fuel oil. The comparison suggested potential application of pyrolysis oil for domestic and commercial use.


Assuntos
Poliestirenos , Pirólise , Catálise , Cobre , Temperatura Alta , Hidrocarbonetos , Óxidos
18.
Waste Manag Res ; 38(2): 202-212, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31405341

RESUMO

Due to a huge increase in polymer production, a tremendous increase in municipal solid waste is observed. Every year the existing landfills for disposal of waste polymers decrease and the effective recycling techniques for waste polymers are getting more and more important. In this work pyrolysis of waste polystyrene was performed in the presence of a laboratory synthesized copper oxide. The samples were pyrolyzed at different heating rates that is, 5°Cmin-1, 10°Cmin-1, 15°Cmin-1 and 20°Cmin-1 in a thermogravimetric analyzer in inert atmosphere using nitrogen. Thermogravimetric data were interpreted using various model fitting (Coats-Redfern) and model free methods (Ozawa-Flynn-Wall, Kissinger-Akahira-Sunose and Friedman). Thermodynamic parameters for the reaction were also determined. The activation energy calculated applying Coats-Redfern, Ozawa-Flynn-Wall, Kissinger-Akahira-Sunose and Friedman models were found in the ranges 105-148.48 kJmol-1, 99.41-140.52 kJmol-1, 103.67-149.15 kJmol-1 and 99.93-141.25 kJmol-1, respectively. The lowest activation energy for polystyrene degradation in the presence of copper oxide indicates the suitability of catalyst for the decomposition reaction to take place at lower temperature. Moreover, the obtained kinetics and thermodynamic parameters would be very helpful in determining the reaction mechanism of the solid waste in a real system.


Assuntos
Poliestirenos , Resíduos Sólidos , Calefação , Cinética , Termogravimetria
19.
Pak J Pharm Sci ; 33(6): 2667-2677, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33867345

RESUMO

Gentamicin sulfate (GEN), a well-known broad-spectrum antibiotic is mostly administered through intramuscular injections and entirely excreted in un-metabolized form through urination from patient's body. Quantitative detection of GEN by direct UV absorption is usually challenging due to lack of chromophores and fluorophores in structure. The current study described the hesperidin coated silver nanoparticles (HSPAgNPs) based novel colorimetric quantitative assay for GEN. HSPAgNPs, based colorimetric detection involved a transition from characteristic yellow colour to blackish brown upon addition of GEN, accompanied by a significant quenching in localized surface plasmon resonance (LSPR) band at λmax 398 nm. Moreover, the synthesized HSPAgNPs were employed to rapid and quantitative detection of GEN in concentration range of 5 to 100 µM. Limit of detection (LOD) and limit of quantification (LOQ) was calculated by standard deviation of the ordinate intercept and slope of the regression line and estimated to be 6.89 µM and 20.88 µM respectively, with a linear correlation factor R2 equal to 0.9990 which strictly followed Beer's law. Furthermore, the utility and effectiveness of HSPAgNPs was also explored for selective recognition of GEN in tap water, serum, human blood plasma and urine.


Assuntos
Gentamicinas/análise , Hesperidina/química , Nanopartículas Metálicas/química , Prata/química , Espectrofotometria Ultravioleta/métodos , Calibragem , Difusão Dinâmica da Luz , Gentamicinas/sangue , Gentamicinas/urina , Química Verde , Hesperidina/isolamento & purificação , Humanos , Concentração de Íons de Hidrogênio , Limite de Detecção , Microscopia Eletrônica de Varredura , Espectroscopia de Infravermelho com Transformada de Fourier , Ressonância de Plasmônio de Superfície
20.
Pak J Pharm Sci ; 33(4(Supplementary)): 1823-1832, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33612466

RESUMO

The aim of this study was to evaluate the protective activity of rutin, and its gold nanoparticles (Ru-AuNPs) in rhabdomyolysis-induced acute kidney injury (AKI) model in mice. Rutin (25 and 50 mg/kg) and Ru-AuNPs (15 and 25 mg/kg) were administered to the animals for four (4) days with water deprivation for 24 hours followed by 50% glycerol injection at the dose of 10 ml/kg intramuscularly. On the next day, animals were dissected and blood and kidneys were collected. Biochemical investigations were performed to evaluate kidney functions, histological studies were carried out to see the changes at tissue level and real-time RT-PCR studies for nuclear factor-κB p50, NFκB; inducible nitric oxide synthase, iNOS; heme oxygenase-1, HO-1; interleukin-6, IL-6; and kidney injury molecule-1, Kim-1 were performed to elucidate the molecular mechanisms. Blood urea and creatinine were found to be decreased in animals treated with rutin and Ru-AuNPs. Down regulation of the mRNA expressions of iNOS, IL-6 and NFkB p50 and up-regulation of Kim-1 and HO-1 genes were observed. The efficacy of Ru-AuNPs was better than rutin alone even at a dose far less than the compound. Rutin and Ru-AuNPs alleviates kidney injury and inflammation in rhabdomyolysis-induced AKI model via anti-inflammatory and anti-oxidant pathways which make it a plausible compound for future studies.


Assuntos
Injúria Renal Aguda/tratamento farmacológico , Regulação para Baixo/efeitos dos fármacos , Heme Oxigenase-1/metabolismo , Receptor Celular 1 do Vírus da Hepatite A/metabolismo , Proteínas de Membrana/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Rutina/farmacologia , Regulação para Cima/efeitos dos fármacos , Injúria Renal Aguda/etiologia , Injúria Renal Aguda/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Ouro/química , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Nanopartículas Metálicas/química , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Rabdomiólise/complicações , Rabdomiólise/metabolismo
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