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1.
Int. microbiol ; 22(2): 239-246, jun. 2019. ilus, graf, tab
Artigo em Inglês | IBECS | ID: ibc-184830

RESUMO

Silver nanoparticles (SN) have been recently developed as a new class of antimicrobial agents against numerous pathogenic microorganisms. SN have also been used as efficient drug delivery systems and have been linked with increasing drug potency. Here, we demonstrated the enhanced antifungal efficacy of nystatin (NYT) and fluconazole (FLU) after conjugation with SN. The antifungal bioactivity of NYT- and FLU-coated SN was evaluated against Candida albicans ATCC 10231 and Aspergillus brasiliensis ATCC 16404 by the agar tube dilution method. The aim of this study was to determine and compare the antifungal efficacy of NYT and FLU with their SN and, finally, the combination of both nanoparticles as NYT-SN + FLU-SN against pathogenic fungi. The results indicated that all test samples showed a dose-dependent response against tested fungi. SN significantly enhanced the antifungal effects of NYT and FLU as compared to drugs alone. We observed a remarkable increase in the percent inhibition of both fungi (90-100%) when treated with a combination of both nanoparticles NYT-SN + FLU-SN at 200 μg/mL only. Furthermore, the morphological modifications occurred at the surface of fungal species were also analyzed by atomic force microscopy (AFM) and scanning electron microscopy (SEM). While tested against primary human cell line, all SN showed negligible cytotoxicity. Hence, these results suggest that the combination of SN with NYT and FLU may have clinical implications in the treatment of fungal infections. However, in vivo studies are needed before recommending the use of these nanoparticles safely in clinical situations


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Assuntos
Antifúngicos/farmacologia , Aspergillus/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Sinergismo Farmacológico , Nanopartículas Metálicas , Prata/farmacologia , Fluconazol/farmacologia , Nistatina/farmacologia , Aspergillus/ultraestrutura , Candida albicans/ultraestrutura , Testes de Sensibilidade Microbiana , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Propriedades de Superfície/efeitos dos fármacos
2.
Int Microbiol ; 22(2): 239-246, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30810990

RESUMO

Silver nanoparticles (SN) have been recently developed as a new class of antimicrobial agents against numerous pathogenic microorganisms. SN have also been used as efficient drug delivery systems and have been linked with increasing drug potency. Here, we demonstrated the enhanced antifungal efficacy of nystatin (NYT) and fluconazole (FLU) after conjugation with SN. The antifungal bioactivity of NYT- and FLU-coated SN was evaluated against Candida albicans ATCC 10231 and Aspergillus brasiliensis ATCC 16404 by the agar tube dilution method. The aim of this study was to determine and compare the antifungal efficacy of NYT and FLU with their SN and, finally, the combination of both nanoparticles as NYT-SN + FLU-SN against pathogenic fungi. The results indicated that all test samples showed a dose-dependent response against tested fungi. SN significantly enhanced the antifungal effects of NYT and FLU as compared to drugs alone. We observed a remarkable increase in the percent inhibition of both fungi (90-100%) when treated with a combination of both nanoparticles NYT-SN + FLU-SN at 200 µg/mL only. Furthermore, the morphological modifications occurred at the surface of fungal species were also analyzed by atomic force microscopy (AFM) and scanning electron microscopy (SEM). While tested against primary human cell line, all SN showed negligible cytotoxicity. Hence, these results suggest that the combination of SN with NYT and FLU may have clinical implications in the treatment of fungal infections. However, in vivo studies are needed before recommending the use of these nanoparticles safely in clinical situations.


Assuntos
Antifúngicos/farmacologia , Aspergillus/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Sinergismo Farmacológico , Fluconazol/farmacologia , Nanopartículas Metálicas , Nistatina/farmacologia , Prata/farmacologia , Aspergillus/ultraestrutura , Candida albicans/ultraestrutura , Testes de Sensibilidade Microbiana , Microscopia de Força Atômica , Microscopia Eletrônica de Varredura , Propriedades de Superfície/efeitos dos fármacos
3.
Antibiotics (Basel) ; 7(4)2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30445704

RESUMO

This paper sets out to determine whether silver nanoparticles conjugation enhance the antibacterial efficacy of clinically approved drugs. Silver conjugated Cephradine and Vildagliptin were synthesized and thoroughly characterized by ultraviolet visible spectrophotometry (UV-vis), Fourier transform infrared (FT-IR) spectroscopic methods, atomic force microscopy (AFM), and dynamic light scattering (DLS) analysis. Using antibacterial assays, the effects of drugs alone and drugs-conjugated with silver nanoparticles were tested against a variety of Gram-negative and Gram-positive bacteria including neuropathogenic Escherichia coli K1, Pseudomonas aeruginosa, Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus (MRSA), Bacillus cereus and Streptococcus pyogenes. Cytopathogenicity assays were performed to determine whether pretreatment of bacteria with drugs inhibit bacterial-mediated host cell cytotoxicity. The UV-vis spectra of both silver-drug nanoconjugates showed a characteristic surface plasmon resonance band in the range of 400⁻450 nm. AFM further confirmed the morphology of nanoparticles and revealed the formation of spherical nanoparticles with size distribution of 30⁻80 nm. FT-IR analysis demonstrated the involvement of Hydroxyl groups in both drugs in the stabilization of silver nanoparticles. Antibacterial assays showed that silver nanoparticle conjugation enhanced antibacterial potential of both Cephradine and Vildagliptin compared to the drugs alone. Pretreatment of bacteria with drugs inhibited E. coli K1-mediated host cell cytotoxicity. In summary, conjugation with silver nanoparticle enhanced antibacterial effects of clinically approved Cephradine. These findings suggest that modifying and/or repurposing clinically approved drugs using nanotechnology is a feasible approach in our search for effective antibacterial molecules.

4.
Int Immunopharmacol ; 59: 310-317, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29679855

RESUMO

Numerous studies have suggested that nuclear factor-κB (NF-κB) and inducible nitric oxide synthase (iNOS) are important mediators of inflammatory response in human and animal models of arthritis. Besides, oxidative stress markers, nitric oxide (NO) and peroxide (PO) are also major contributors in the pathogenesis of rheumatoid arthritis (RA). Over expression of these inflammatory mediators leads to the extracellular matrix degradation, and excessive cartilage and bone resorption, ultimately leading to the irreversible damage to joints. The aim of the present study was to investigate the anti-arthritic mechanism of bioflavonoids, rutin and rutin-conjugated gold nanoparticles (R-AuNPs) by determining their role in the modulation of NF-κB and iNOS expression in collagen-induced arthritis (CIA) model of rats. Arthritis was induced by the subcutaneous administration of bovine type II collagen. Treatment was started with rutin, indomethacin + rutin (I + R) and R-AuNPs on the day of CIA induction. The severity of arthritis was determined by measuring the arthritic score on alternate days until mean arthritic score of 4 was observed. The NO and PO levels were also analyzed in serum samples. NF-κB and iNOS expression levels were determined in spleen tissue samples by real time RT-PCR and immunohistochemistry. Marked reduction in the arthritic score as well as in the NO and PO levels was observed in the treated groups. A significant downregulation in the NF-κB and iNOS expression levels was also observed in the treatment groups compared to the arthritic control group. Collectively, the findings suggest potential clinical role of rutin and R-AuNPs in the treatment of rheumatoid arthritis.


Assuntos
Anti-Inflamatórios , Artrite Experimental/tratamento farmacológico , Ouro , Nanopartículas Metálicas , NF-kappa B/antagonistas & inibidores , Óxido Nítrico Sintase Tipo II/antagonistas & inibidores , Rutina , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Artrite Experimental/metabolismo , Regulação para Baixo , Feminino , Ouro/farmacologia , Ouro/uso terapêutico , Nanopartículas Metálicas/uso terapêutico , NF-kappa B/genética , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Ratos Wistar , Rutina/farmacologia , Rutina/uso terapêutico , Baço/efeitos dos fármacos , Baço/metabolismo
5.
Parasitol Res ; 117(1): 265-271, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29218442

RESUMO

Infectious diseases are the leading cause of morbidity and mortality, killing more than 15 million people worldwide. This is despite our advances in antimicrobial chemotherapy and supportive care. Nanoparticles offer a promising technology to enhance drug efficacy and formation of effective vehicles for drug delivery. Here, we conjugated amphotericin B, nystatin (macrocyclic polyenes), and fluconazole (azole) with silver nanoparticles. Silver-conjugated drugs were synthesized successfully and characterized by ultraviolet-visible spectrophotometry, Fourier transform infrared spectroscopy, and atomic force microscopy. Conjugated and unconjugated drugs were tested against Acanthamoeba castellanii belonging to the T4 genotype using amoebicidal assay and host cell cytotoxicity assay. Viability assays revealed that silver nanoparticles conjugated with amphotericin B (Amp-AgNPs) and nystatin (Nys-AgNPs) exhibited significant antiamoebic properties compared with drugs alone or AgNPs alone (P < 0.05) as determined by Trypan blue exclusion assay. In contrast, conjugation of fluconazole with AgNPs had limited effect on its antiamoebic properties. Notably, AgNP-coated drugs inhibited amoebae-mediated host cell cytotoxicity as determined by measuring lactate dehydrogenase release. Overall, here we present the development of a new formulation of more effective antiamoebic agents based on AgNPs coated with drugs that hold promise for future applications.


Assuntos
Amebíase/tratamento farmacológico , Amebicidas/farmacologia , Anfotericina B/farmacologia , Fluconazol/farmacologia , Nanopartículas Metálicas/química , Nistatina/farmacologia , Acanthamoeba castellanii/efeitos dos fármacos , Acanthamoeba castellanii/genética , Amebíase/parasitologia , Amebicidas/química , Anfotericina B/química , Fluconazol/química , Humanos , Microscopia de Força Atômica , Nistatina/química , Prata/química , Espectrofotometria Ultravioleta , Espectroscopia de Infravermelho com Transformada de Fourier
6.
AMB Express ; 7(1): 210, 2017 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-29164404

RESUMO

Biofilm formation by pathogenic bacteria is one of the major threats in hospital related infections, hence inhibiting and eradicating biofilms has become a primary target for developing new anti-infection approaches. The present study was aimed to develop novel antibiofilm agents against two Gram-positive bacteria; Staphylococcus aureus (ATCC 43300) and Streptococcus mutans (ATCC 25175) using gold nanomaterials conjugated with 3-(diphenylphosphino)propionic acid (Au-LPa). Gold nanomaterials with different sizes as 2-3 nm small and 9-90 nm (50 nm average size) large were stabilized by LPa via different chemical synthetic strategies. The nanomaterials were fully characterized using atomic force microscope (AFM), transmission electron microscope, ultraviolet-visible absorption spectroscopy, and Fourier transformation infrared spectroscopy. Antibiofilm activity of Au-LPa nanomaterials was tested using LPa alone, Au-LPa and unprotected gold nanomaterials against the both biofilm-producing bacteria. The results showed that LPa alone did not inhibit biofilm formation to a significant extent below 0.025 mM, while conjugation with gold nanomaterials displayed manifold enhanced antibiofilm potential against both strains. Moreover, it was also observed that the antibiofilm potency of the Au-LPa nanomaterials varies with size variations of nanomaterials. AFM analysis of biofilms further complemented the assay results and provided morphological aspects of the antibiofilm action of Au-LPa nanomaterials.

7.
J Hazard Mater ; 309: 97-106, 2016 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-26878705

RESUMO

A novel fluorescent bis-calix[4]arene macrocycle 9 incorporating metal-binding pockets was successfully prepared. The structure of macrocycle 9 and its precursors were characterized via EI-MS, MALDI-TOF-MS, ESI-MS, (1)H NMR, (13)CNMR, 2D NMR, and X-ray crystallography. The macrocycle 9 displayed selective fluorescence quenching after interacting with Cu(2+) in the presence competing metal cations including Mg(2+), Ca(2+), Ba(2+), Ag(+), Zn(2+), Ti(4+),Cd(2+), Hg(2+), Pb(2+), In(3+), La(3+), Cr(3+), Ni(2+), Sb(3+), V(5+), Fe(3+), Co(2+), Sn(2+), Sn(2+), and Tl(+). The Cu(2+) limit of detection was found to be 40 nM much lower than its threshold level (∼ 20 µM) in drinking water permitted by the U.S Environmental Protection Agency (EPA). Furthermore, drinking water samples from Karachi University (Pakistan) spiked with Cu(2+) were analysed with the sensing system and the results showed an excellent agreement with the fluorescence quenching phenomenon of macrocycle 9 examined in deionized water. Importantly, the chemosensor 9 could be used to detect Cu(2+) in living cells.

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