Displaying publications 141 - 160 of 1338 in total

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  1. Fulltext Antiamoebic activity of plant-based natural products and their conjugated silver nanoparticles against Acanthamoeba castellanii (ATCC 50492)
    Anwar A, Ting ELS, Anwar A, Ain NU, Faizi S, Shah MR, et al.
    AMB Express, 2020 Feb 03;10(1):24.
    PMID: 32016777 DOI: 10.1186/s13568-020-0960-9
    Acanthamoeba spp. are the causative agent of Acanthamoeba keratitis and granulomatous amoebic encephalitis (GAE). The current options to treat Acanthamoeba infections have limited success. Silver nanoparticles show antimicrobial effects and enhance the efficacy of their payload at the specific biological targets. Natural folk plants have been widely used for treating diseases as the phytochemicals from several plants have been shown to exhibit amoebicidal effects. Herein, we used natural products of plant or commercial sources including quercetin (QT), kolavenic acid (PGEA) isolated from plant extracts of Polyalthia longifolia var pendula and crude plant methanolic extract of Caesalpinia pulcherrima (CPFLM) as antiacanthamoebic agents. Furthermore, these plant-based materials were conjugated with silver nanoparticles (AgNPs) to determine the effects of the natural compounds and their nanoconjugates against a clinical isolate of A. castellanii from a keratitis patient (ATCC 50492) belonging to the T4 genotype. The compounds were conjugated with AgNPs and characterized by using ultraviolet visible spectrophotometry and atomic force microscopy. Quercetin coated silver nanoparticles (QT-AgNPs) showed characteristic surface plasmon resonance band at 443 nm and the average size distribution was found to be around 45 nm. The natural compounds alone and their nanoconjugates were tested for the viability of amoebae, encystation and excystation activity against A. castellanii. The natural compounds showed significant growth inhibition of A. castellanii while QT-AgNPs specifically exhibited enhanced antiamoebic effects as well as interrupted the encystation and excystation activity of the amoebae. Interestingly, these compounds and nanoconjugates did not exhibit in vitro cytotoxic effects against human cells. Plant-based compounds and extracts could be an interesting strategy in development of alternative therapeutics against Acanthamoeba infections.
    Matched MeSH terms: Metal Nanoparticles
  2. Fulltext Antidiabetic Drugs and Their Nanoconjugates Repurposed as Novel Antimicrobial Agents against Acanthamoeba castellanii
    Anwar A, Siddiqui R, Raza Shah M, Khan NA
    J Microbiol Biotechnol, 2019 May 28;29(5):713-720.
    PMID: 31030451 DOI: 10.4014/jmb/1903.03009
    Acanthamoeba castellanii belonging to the T4 genotype may cause a fatal brain infection known as granulomatous amoebic encephalitis, and the vision-threatening eye infection Acanthamoeba keratitis. The aim of this study was to evaluate the antiamoebic effects of three clinically available antidiabetic drugs, Glimepiride, Vildagliptin and Repaglinide, against A. castellanii belonging to the T4 genotype. Furthermore, we attempted to conjugate these drugs with silver nanoparticles (AgNPs) to enhance their antiamoebic effects. Amoebicidal, encystation, excystation, and host cell cytotoxicity assays were performed to unravel any antiacanthamoebic effects. Vildagliptin conjugated silver nanoparticles (Vgt-AgNPs) characterized by spectroscopic techniques and atomic force microscopy were synthesized. All three drugs showed antiamoebic effects against A. castellanii and significantly blocked the encystation. These drugs also showed significant cysticidal effects and reduced host cell cytotoxicity caused by A. castellanii. Moreover, Vildagliptin-coated silver nanoparticles were successfully synthesized and are shown to enhance its antiacanthamoebic potency at significantly reduced concentration. The repurposed application of the tested antidiabetic drugs and their nanoparticles against free-living amoeba such as Acanthamoeba castellanii described here is a novel outcome that holds tremendous potential for future applications against devastating infection.
    Matched MeSH terms: Metal Nanoparticles/chemistry
  3. Fulltext Gold Nanoparticle-Conjugated Cinnamic Acid Exhibits Antiacanthamoebic and Antibacterial Properties
    Anwar A, Siddiqui R, Shah MR, Khan NA
    Antimicrob Agents Chemother, 2018 09;62(9).
    PMID: 29967024 DOI: 10.1128/AAC.00630-18
    trans-Cinnamic acid (CA) is a natural organic compound. Using amoebicidal assays, for the first time we showed that CA affected the viability of the protist pathogen Acanthamoeba castellanii Conjugation with gold nanoparticles (AuNPs) enhanced the antiamoebic effects of CA. CA-coated AuNPs (CA-AuNPs) also exhibited significant excystation and encystation activity, compared to CA and AuNPs alone. Pretreatment of amoebae with CA-AuNPs inhibited A. castellanii-mediated host cell cytotoxicity. Moreover, CA-AuNPs exhibited potent effects against methicillin-resistant Staphylococcus aureus and neuropathogenic Escherichia coli K1 and protected host cells against bacteria-mediated host cell death.
    Matched MeSH terms: Metal Nanoparticles/administration & dosage*
  4. Pyrazinium thioacetate capped gold nanoparticles as Fe(III) sensor and Fe(III) marked anti-proliferating agent in human neuroblastoma cells
    Anwar A, Minhaz A, Hussain SS, Anwar A, Simjee SU, Ishaq M, et al.
    Spectrochim Acta A Mol Biomol Spectrosc, 2019 Jan 05;206:135-140.
    PMID: 30096697 DOI: 10.1016/j.saa.2018.07.099
    Gold nanoparticles (AuNPs) stabilized by new cationic 1‑(3‑(acetylthio)propyl)pyrazin‑1‑ium ligand (PPTA) were synthesized. AuNPs stabilized by PPTA (PPTA-AuNPs) were found to be spherical and polydispersed with the average size of 60 nm. Human neuroblastoma (SHSY-5Y) cells permeability of PPTA-AuNPs was found to be a key feature to study the intracellular quenching of Fe(III) proliferative activity. In vitro MTT assay revealed non-cytotoxicity of PPTA and PPTA-AuNPs at 100 μM concentration, while treatment of 100 μM of Fe(III) with SHSY-5Y cells resulted into higher cells viability. Contrary, a mixture of 1:1 Fe(III) with PPTA-AuNPs showed no change in the viability of cells at same concentration which suggests the intracellular complexation and recognition of Fe(III) by PPTA-AuNPs. AFM morphological analysis of SHSY-5Y cells also supported the MTT assay results, and it is safe to conclude that PPTA-AuNPs can be used as Fe(III) probes in living cells. In addition, Fe(III) caused a significant decrease in the absorbance of surface plasmon resonance (SPR) band of PPTA-AuNPs in a wide range of concentration and pH, with limit of detection 4.3 μM. Moreover, the specific response of PPTA-AuNPs towards Fe(III) was unaffected by the interference of other metals and components of real samples of tap water.
    Matched MeSH terms: Metal Nanoparticles/chemistry
  5. Clinically Approved Drugs against CNS Diseases as Potential Therapeutic Agents To Target Brain-Eating Amoebae
    Anwar A, Rajendran K, Siddiqui R, Raza Shah M, Khan NA
    ACS Chem Neurosci, 2019 01 16;10(1):658-666.
    PMID: 30346711 DOI: 10.1021/acschemneuro.8b00484
    Central nervous system (CNS) infections caused by free-living amoebae such as Acanthamoeba species and Naegleria fowleri are rare but fatal. A major challenge in the treatment against the infections caused by these amoebae is the discovery of novel compounds that can effectively cross the blood-brain barrier to penetrate the CNS. It is logical to test clinically approved drugs against CNS diseases for their potential antiamoebic effects since they are known for effective blood-brain barrier penetration and affect eukaryotic cell targets. The antiamoebic effects of clinically available drugs for seizures targeting gamma-amino butyric acid (GABA) receptor and ion channels were tested against Acanthamoeba castellanii belonging to the T4 genotype and N. fowleri. Three such drugs, namely, diazepam (Valium), phenobarbitone (Luminal), phenytoin (Dilantin), and their silver nanoparticles (AgNPs) were evaluated against both trophozoites and cysts stage. Drugs alone and drug conjugated silver nanoparticles were tested for amoebicidal, cysticidal, and host-cell cytotoxicity assays. Nanoparticles were synthesized by sodium borohydride reduction of silver nitrate with drugs as capping agents. Drug conjugated nanoconjugates were characterized by ultraviolet-visible (UV-vis) and Fourier transform infrared (FT-IR) spectroscopies and atomic force microscopy (AFM). In vitro moebicidal assay showed potent amoebicidal effects for diazepam, phenobarbitone, and phenytoin-conjugated AgNPs as compared to drugs alone against A. castellanii and N. fowleri. Furthermore, both drugs and drug conjugated AgNPs showed compelling cysticidal effects. Drugs conjugations with silver nanoparticles enhanced their antiacanthamoebic activity. Interestingly, amoeba-mediated host-cell cytotoxicity was also significantly reduced by drugs alone as well as their nanoconjugates. Since, these drugs are being used to target CNS diseases, their evaluation against brain-eating amoebae seems feasible due to advantages such as permeability of the blood-brain barrier, established pharmacokinetics and dynamics, and United States Food and Drug Administration (FDA) approval. Given the limited availability of effective drugs against brain-eating amoebae, the clinically available drugs tested here present potential for further in vivo studies.
    Matched MeSH terms: Metal Nanoparticles/parasitology
  6. Fulltext Gold Nanoparticles Conjugation Enhances Antiacanthamoebic Properties of Nystatin, Fluconazole and Amphotericin B
    Anwar A, Siddiqui R, Raza Shah M, Ahmed Khan N
    J Microbiol Biotechnol, 2019 Jan 28;29(1):171-177.
    PMID: 30415525 DOI: 10.4014/jmb.1805.05028
    Parasitic infections have remained a significant burden on human and animal health. In part, this is due to lack of clinically-approved, novel antimicrobials and a lack of interest by the pharmaceutical industry. An alternative approach is to modify existing clinically-approved drugs for efficient delivery formulations to ensure minimum inhibitory concentration is achieved at the target site. Nanotechnology offers the potential to enhance the therapeutic efficacy of drugs through modification of nanoparticles with ligands. Amphotericin B, nystatin, and fluconazole are clinically available drugs in the treatment of amoebal and fungal infections. These drugs were conjugated with gold nanoparticles. To characterize these gold-conjugated drug, atomic force microscopy, ultraviolet-visible spectrophotometry and Fourier transform infrared spectroscopy were performed. These drugs and their gold nanoconjugates were examined for antimicrobial activity against the protist pathogen, Acanthamoeba castellanii of the T4 genotype. Moreover, host cell cytotoxicity assays were accomplished. Cytotoxicity of these drugs and drug-conjugated gold nanoparticles was also determined by lactate dehydrogenase assay. Gold nanoparticles conjugation resulted in enhanced bioactivity of all three drugs with amphotericin B producing the most significant effects against Acanthamoeba castellanii (p ＜ 0.05). In contrast, bare gold nanoparticles did not exhibit antimicrobial potency. Furthermore, amoebae treated with drugs-conjugated gold nanoparticles showed reduced cytotoxicity against HeLa cells. In this report, we demonstrated the use of nanotechnology to modify existing clinically-approved drugs and enhance their efficacy against pathogenic amoebae. Given the lack of development of novel drugs, this is a viable approach in the treatment of neglected diseases.
    Matched MeSH terms: Metal Nanoparticles
  7. Effects of Shape and Size of Cobalt Phosphate Nanoparticles against Acanthamoeba castellanii
    Anwar A, Chi Fung L, Anwar A, Jagadish P, Numan A, Khalid M, et al.
    Pathogens, 2019 Nov 22;8(4).
    PMID: 31766722 DOI: 10.3390/pathogens8040260
    T4 genotype Acanthamoeba are opportunistic pathogens that cause two types of infections, including vision-threatening Acanthamoeba keratitis (AK) and a fatal brain infection known as granulomatous amoebic encephalitis (GAE). Due to the existence of ineffective treatments against Acanthamoeba, it has become a potential threat to all contact lens users and immunocompromised patients. Metal nanoparticles have been proven to have various antimicrobial properties against bacteria, fungi, and parasites. Previously, different types of cobalt nanoparticles showed some promise as anti-acanthamoebic agents. In this study, the objectives were to synthesize and characterize the size, morphology, and crystalline structure of cobalt phosphate nanoparticles, as well as to determine the effects of different sizes of cobalt metal-based nanoparticles against A. castellanii. Cobalt phosphate octahydrate (CHP), Co3(PO4)2•8H2O, was synthesized by ultrasonication using a horn sonicator, then three different sizes of cobalt phosphates Co3(PO4)2 were produced through calcination of Co3(PO4)2•8H2O at 200 °C, 400 °C and 600 °C (CP2, CP4, CP6). These three types of cobalt phosphate nanoparticles were characterized using a field emission scanning electron microscope (FESEM), energy dispersive X-ray spectroscopy (EDX), and X-ray diffraction (XRD) analysis. Next, the synthesized nanoparticles were subjected to biological assays to investigate their amoebicidal, amoebistatic, anti-encystation, and anti-excystation effects against A. castellanii, as well as cell cytotoxicity. The overall results showed that 1.30 ± 0.70 µm of CHP microflakes demonstrated the best anti-acanthemoebic effects at 100 µg/mL, followed by 612.50 ± 165.94 nm large CP6 nanograins. However, amongst the three tested cobalt phosphates, Co3(PO4)2, the smaller nanoparticles had stronger antiamoebic effects against A. castellanii. During cell cytotoxicity analysis, CHP exhibited only 15% cytotoxicity against HeLa cells, whereas CP6 caused 46% (the highest) cell cytotoxicity at the highest concentration, respectively. Moreover, the composition and morphology of nanoparticles is suggested to be important in determining their anti-acathamoebic effects. However, the molecular mechanisms of cobalt phosphate nanoparticles are still unidentified. Nevertheless, the results suggested that cobalt phosphate nanoparticles hold potential for development of nanodrugs against Acanthamoeba.
    Matched MeSH terms: Metal Nanoparticles
  8. Oleic acid-conjugated silver nanoparticles as efficient antiamoebic agent against Acanthamoeba castellanii
    Anwar A, Abdalla SAO, Aslam Z, Shah MR, Siddiqui R, Khan NA
    Parasitol Res, 2019 Jul;118(7):2295-2304.
    PMID: 31093751 DOI: 10.1007/s00436-019-06329-3
    Acanthamoeba castellanii belonging to the T4 genotype is an opportunistic pathogen which is associated with blinding eye keratitis and rare but fatal central nervous system infection. A. castellanii pose serious challenges in antimicrobial chemotherapy due to its ability to convert into resistant, hardy shell-protected cyst form that leads to infection recurrence. The fatty acid composition of A. castellanii trophozoites is known to be most abundant in oleic acid which chemically is an unsaturated cis-9-Octadecanoic acid and naturally found in animal and vegetable fats and oils. This study was designed to evaluate antiacanthamoebic effects of oleic acid against trophozoites, cysts as well as parasite-mediated host cell cytotoxicity. Moreover, oleic acid-conjugated silver nanoparticles (AgNPs) were also synthesized and tested against A. castellanii. Oleic acid-AgNPs were synthesized by chemical reduction method and characterized by ultraviolet-visible spectrophotometry, atomic force microscopy, dynamic light scattering analysis, and Fourier transform infrared spectroscopy. Viability, growth inhibition, encystation, and excystation assays were performed with 10 and 5 μM concentration of oleic acid alone and oleic acid-conjugated AgNPs. Bioassays revealed that oleic acid alone and oleic acid-conjugated AgNPs exhibited significant antiamoebic properties, whereas nanoparticle conjugation further enhanced the efficacy of oleic acid. Phenotype differentiation assays also showed significant inhibition of encystation and excystation at 5 μM. Furthermore, oleic acid and oleic acid-conjugated AgNPs also inhibited amoebae-mediated host cell cytotoxicity as determined by lactate dehydrogenase release. These findings for the first time suggest that oleic acid-conjugated AgNPs exhibit antiacanthamoebic activity that hold potential for therapeutic applications against A. castellanii.
    Matched MeSH terms: Metal Nanoparticles/chemistry*
  9. Fulltext Antimicrobial activities of green synthesized gums-stabilized nanoparticles loaded with flavonoids
    Anwar A, Masri A, Rao K, Rajendran K, Khan NA, Shah MR, et al.
    Sci Rep, 2019 02 28;9(1):3122.
    PMID: 30816269 DOI: 10.1038/s41598-019-39528-0
    Herein, we report green synthesized nanoparticles based on stabilization by plant gums, loaded with citrus fruits flavonoids Hesperidin (HDN) and Naringin (NRG) as novel antimicrobial agents against brain-eating amoebae and multi-drug resistant bacteria. Nanoparticles were thoroughly characterized by using zetasizer, zeta potential, atomic force microscopy, ultravoilet-visible and Fourier transform-infrared spectroscopic techniques. The size of these spherical nanoparticles was found to be in the range of 100-225 nm. The antiamoebic effects of these green synthesized Silver and Gold nanoparticles loaded with HDN and NRG were tested against Acanthamoeba castellanii and Naegleria fowleri, while antibacterial effects were evaluated against methicillin-resistant Staphylococcus aureus (MRSA) and neuropathogenic Escherichia coli K1. Amoebicidal assays revealed that HDN loaded Silver nanoparticles stabilized by gum acacia (GA-AgNPs-HDN) quantitatively abolished amoeba viability by 100%, while NRG loaded Gold nanoparticles stabilized by gum tragacanth (GT-AuNPs-NRG) significantly reduced the viability of A. castellanii and N. fowleri at 50 µg per mL. Furthermore, these nanoparticles inhibited the encystation and excystation by more than 85%, as well as GA-AgNPs-HDN only completely obliterated amoeba-mediated host cells cytopathogenicity. Whereas, GA-AgNPs-HDN exhibited significant bactericidal effects against MRSA and E. coli K1 and reduced bacterial-mediated host cells cytotoxicity. Notably, when tested against human cells, these nanoparticles showed minimal (23%) cytotoxicity at even higher concentration of 100 µg per mL as compared to 50 µg per mL used for antimicrobial assays. Hence, these novel nanoparticles formulations hold potential as therapeutic agents against infections caused by brain-eating amoebae, as well as multi-drug resistant bacteria, and recommend a step forward in drug development.
    Matched MeSH terms: Nanoparticles/chemistry*
  10. Fulltext Novel Azoles as Antiparasitic Remedies against Brain-Eating Amoebae
    Anwar A, Mungroo MR, Khan S, Fatima I, Rafique R, Kanwal, et al.
    Antibiotics (Basel), 2020 Apr 17;9(4).
    PMID: 32316387 DOI: 10.3390/antibiotics9040188
    Balamuthia mandrillaris and Naegleriafowleri are opportunistic protozoan pathogens capable of producing infection of the central nervous system with more than 95% mortality rate. Previously, we have synthesized several compounds with antiamoebic properties; however, synthesis of compounds that are analogues of clinically used drugs is a highly desirable approach that can lead to effective drug development against these devastating infections. In this regard, compounds belonging to the azole class possess wide range of antimicrobial properties and used clinically. In this study, six novel benzimidazole, indazole, and tetrazole derivatives were synthesized and tested against brain-eating amoebae. These compounds were tested for their amoebicidal and static properties against N. fowleri and B. mandrillaris. Furthermore, the compounds were conjugated with silver nanoparticles and characterized. The synthetic heterocyclic compounds showed up to 72% and 65% amoebicidal activities against N. fowleri and B. mandrillaris respectively, while expressing up to 75% and 70% amoebistatic activities, respectively. Following conjugation with silver nanoparticles, amoebicidal activities of the drugs increased by up to 46 and 36% versus B. mandrillaris and N. fowleri. Minimal effects were observed when the compounds were evaluated against human cells using cytotoxicity assays. In summary, azole compounds exhibited potent activity against N. fowleri and B. mandrillaris. Moreover, conjugation of the azole compounds with silver nanoparticles further augmented the capabilities of the compounds against amoebae.
    Matched MeSH terms: Metal Nanoparticles
  11. Metformin-coated silver nanoparticles exhibit anti-acanthamoebic activities against both trophozoite and cyst stages
    Anwar A, Soomaroo A, Anwar A, Siddiqui R, Khan NA
    Exp Parasitol, 2020 Aug;215:107915.
    PMID: 32461112 DOI: 10.1016/j.exppara.2020.107915
    Acanthamoeba castellanii is an opportunistic protozoan responsible for serious human infections including Acanthamoeba keratitis and granulomatous amoebic encephalitis. Despite advances in antimicrobial therapy and supportive care, infections due to Acanthamoeba are a major public concern. Current methods of treatment are not fully effective against both the trophozoite and cyst forms of A. castellanii and are often associated with severe adverse effects, host cell cytotoxicity and recurrence of infection. Therefore, there is an urgent need to develop new therapeutic approaches for the treatment and management of Acanthamoebic infections. Repurposing of clinically approved drugs is a viable avenue for exploration and is particularly useful for neglected and rare diseases where there is limited interest by pharmaceutical companies. Nanotechnology-based drug delivery systems offer promising approaches in the biomedical field, particularly in diagnosis and drug delivery. Herein, we conjugated an antihyperglycemic drug, metformin with silver nanoparticles and assessed its anti-acanthamoebic properties. Characterization by ultraviolet-visible spectrophotometry and atomic force microscopy showed successful formation of metformin-coated silver nanoparticles. Amoebicidal and amoebistatic assays revealed that metformin-coated silver nanoparticles reduced the viability and inhibited the growth of A. castellanii significantly more than metformin and silver nanoparticles alone at both 5 and 10 μM after 24 h incubation. Metformin-coated silver nanoparticles also blocked encystation and inhibited the excystation in Acanthamoeba after 72 h incubation. Overall, the conjugation of metformin with silver nanoparticles was found to enhance its antiamoebic effects against A. castellanii. Furthermore, the pretreatment of A. castellanii with metformin and metformin-coated silver nanoparticles for 2 h also reduced the amoebae-mediated host cell cytotoxicity after 24 h incubation from 73% to 10% at 10 μM, indicating that the drug-conjugated silver nanoparticles confer protection to human cells. These findings suggest that metformin-coated silver nanoparticles hold promise in the improved treatment and management of Acanthamoeba infections.
    Matched MeSH terms: Metal Nanoparticles/administration & dosage; Metal Nanoparticles/therapeutic use
  12. Antiamoebic activity of synthetic tetrazoles against Acanthamoeba castellanii belonging to T4 genotype and effects of conjugation with silver nanoparticles
    Anwar A, Yi YP, Fatima I, Khan KM, Siddiqui R, Khan NA, et al.
    Parasitol Res, 2020 Jun;119(6):1943-1954.
    PMID: 32385711 DOI: 10.1007/s00436-020-06694-4
    Acanthamoeba causes diseases such as Acanthamoeba keratitis (AK) which leads to permanent blindness and granulomatous Acanthamoeba encephalitis (GAE) where there is formation of granulomas in the brain. Current treatments such as chlorhexidine, diamidines, and azoles either exhibit undesirable side effects or require immediate and prolonged treatment for the drug to be effective or prevent relapse. Previously, antifungal drugs amphotericin B, nystatin, and fluconazole-conjugated silver with nanoparticles have shown significantly increased activity against Acanthamoeba castellanii. In this study, two functionally diverse tetrazoles were synthesized, namely 5-(3-4-dimethoxyphenyl)-1H-tetrazole and 1-(3-methoxyphenyl)-5-phenoxy-1H-tetrazole, denoted by T1 and T2 respectively. These compounds were evaluated for anti-Acanthamoeba effects at different concentrations ranging from 5 to 50 μM. Furthermore, these compounds were conjugated with silver nanoparticles (AgNPs) to enhance their efficacy. Particle size analysis showed that T1-AgNPs and T2-AgNPs had an average size of 52 and 70 nm respectively. After the successful synthesis and characterization of tetrazoles and tetrazole-conjugated AgNPs, they were subjected to anti-Acanthamoeba studies. Amoebicidal assay showed that at concentration 10 μM and above, T2 showed promising antiamoebic activities between the two compounds while encystation and excystation assays reveal that both T1 and T2 have inhibited differentiation activity against Acanthamoeba castellanii. Conjugation of T1 and T2 to AgNP also increased efficacy of tetrazoles as anti-Acanthamoeba agents. This may be due to the increased bioavailability as AgNP allows better delivery of treatment compounds to A. castellanii. Human cell cytotoxicity assay revealed that tetrazoles and AgNPs are significantly less toxic towards human cells compared with chlorhexidine which is known to cause undesirable side effects. Cytopathogenicity assay also revealed that T2 conjugated with AgNPs significantly reduced cytopathogenicity of A. castellanii compared with T2 alone, suggesting that T2-conjugated AgNP is an effective and safe anti-Acanthamoeba agent. The use of a synthetic azole compound conjugated with AgNPs can be an alternative strategy for drug development against A. castellanii. However, mechanistic and in vivo studies are needed to explore further translational values.
    Matched MeSH terms: Metal Nanoparticles*
  13. Silver nanoparticle conjugation affects antiacanthamoebic activities of amphotericin B, nystatin, and fluconazole
    Anwar A, Siddiqui R, Hussain MA, Ahmed D, Shah MR, Khan NA
    Parasitol Res, 2018 Jan;117(1):265-271.
    PMID: 29218442 DOI: 10.1007/s00436-017-5701-x
    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 
    Matched MeSH terms: Metal Nanoparticles/chemistry*
  14. Fulltext Synthesis of 4-(dimethylamino)pyridine propylthioacetate coated gold nanoparticles and their antibacterial and photophysical activity
    Anwar A, Khalid S, Perveen S, Ahmed S, Siddiqui R, Khan NA, et al.
    J Nanobiotechnology, 2018 Jan 29;16(1):6.
    PMID: 29378569 DOI: 10.1186/s12951-017-0332-z
    BACKGROUND: Gold nanoparticles are useful candidate for drug delivery applications and are associated with enhancement in the bioavailability of coated drugs and/or therapeutic agent. Since, heterocyclic compounds are known to exhibit antimicrobial potential against variety of pathogens, we designed this study to evaluate the antibacterial effects of gold nanoparticles conjugation with new synthesized cationic ligand; 4-Dimethyl aminopyridinium propylthioacetate (DMAP-PTA) in comparison with pure compound and antibiotic drug Pefloxacin. Antibacterial activity of DMAP-PTA coated gold nanoparticles was investigated against a fecal strain of E. coli (ATCC 8739).

    RESULTS: A new dimethyl aminopyridine based stabilizing agent named as DMAP-PTA was synthesized and used for stabilization of gold nanoparticles. Gold nanoparticles coated with DMAP-PTA abbreviated as DMAP-PTA-AuNPs were thoroughly characterized by UV-visible, FT-IR spectroscopic methods and transmission electron microscope before biological assay. DMAP-PTA, DMAP-PTA-AuNPs and Pefloxacin were examined for their antibacterial potential against E. coli, and the minimum inhibitory concentration (MIC) was determined to be 300, 200 and 50 µg/mL respectively. Gold nanoparticles conjugation was found to significantly enhance the antibacterial activity of DMAP-PTA as compared to pure compound. Moreover, effects of DMAP-PTA-AuNPs on the antibacterial potential of Pefloxacin was also evaluated by combination therapy of 1:1 mixture of DMAP-PTA-AuNPs and Pefloxacin against E. coli in a wide range of concentrations from 5 to 300 µg/mL. The MIC of Pefloxacin + DMAP-PTA-AuNPs mixture was found to be 25 µg/mL as compared to Pefloxacin alone (50 µg/mL), which clearly indicates that DMAP-PTA-AuNPs increased the potency of Pefloxacin. AFM analysis was also carried out to show morphological changes occur in bacteria before and after treatment of test samples. Furthermore, DMAP-PTA-AuNPs showed high selectivity towards Pefloxacin in spectrophotometric drug recognition studies which offers tremendous potential for analytical applications.

    CONCLUSIONS: Gold nanoparticles conjugation was shown to enhance the antibacterial efficacy of DMAP-PTA ligand, while DMAP-PTA-AuNPs also induced synergistic effects on the potency of Pefloxacin against E. coli. DMAP-PTA-AuNPs were also developed as Pefloxacin probes in recognizing the drug in blood and water samples in the presence of other drugs.

    Matched MeSH terms: Metal Nanoparticles/ultrastructure; Metal Nanoparticles/chemistry*
  15. Repositioning of Guanabenz in Conjugation with Gold and Silver Nanoparticles against Pathogenic Amoebae Acanthamoeba castellanii and Naegleria fowleri
    Anwar A, Mungroo MR, Anwar A, Sullivan WJ, Khan NA, Siddiqui R
    ACS Infect Dis, 2019 Dec 13;5(12):2039-2046.
    PMID: 31612700 DOI: 10.1021/acsinfecdis.9b00263
    Brain-eating amoebae cause devastating infections in the central nervous system of humans, resulting in a mortality rate of 95%. There are limited effective therapeutic options available clinically for treating granulomatous amoebic encephalitis and primary amoebic meningoencephalitis caused by Acanthamoeba castellanii (A. castellanii) and Naegleria fowleri (N. fowleri), respectively. Here, we report for the first time that guanabenz conjugated to gold and silver nanoparticles has significant antiamoebic activity against both A. castellanii and N. fowleri. Gold and silver conjugated guanabenz nanoparticles were synthesized by the one-phase reduction method and were characterized by ultraviolet-visible spectrophotometry and atomic force microscopy. Both metals were facilely stabilized by the coating of guanabenz, which was examined by surface plasmon resonance determination. The average size of gold nanoconjugated guanabenz was found to be 60 nm, whereas silver nanoparticles were produced in a larger size distribution with the average diameter of around 100 nm. Guanabenz and its noble metal nanoconjugates exhibited potent antiamoebic effects in the range of 2.5 to 100 μM against both amoebae. Nanoparticle conjugation enhanced the antiamoebic effects of guanabenz, as more potent activity was observed at a lower effective concentration (2.5 and 5 μM) compared to the drug alone. Moreover, encystation and excystation assays revealed that guanabenz inhibits the interconversion between the trophozoite and cyst forms of A. castellanii. Cysticdal effects against N. fowleri were also observed. Notably, pretreatment of A. castellanii with guanabenz and its nanoconjugates exhibited a significant reduction in the host cell cytopathogenicity from 65% to 38% and 2% in case of gold and silver nanoconjugates, respectively. Moreover, the cytotoxic evaluation of guanabenz and its nanoconjugates revealed negligible cytotoxicity against human cells. Guanabenz is already approved for hypertension and crosses the blood-brain barrier; the results of our current study suggest that guanabenz and its conjugated gold and silver nanoparticles can be repurposed as a potential drug for treating brain-eating amoebic infections.
    Matched MeSH terms: Metal Nanoparticles
  16. Synthesis of titanium dioxide nanoparticles via sucrose ester micelle-mediated hydrothermal processing route
    Anwar N, Kassim A, Lim H, Zakarya S, Huang N
    Sains Malaysiana, 2010;39:261-265.
    Titanium dioxide nanoparticles were synthesized via low-temperature sucrose ester micelle-mediated hydrothermal processing route using titanium isopropoxide as the precursor. X-ray diffractometer revealed that the samples possessed a mixed crystalline phases consisting of anatase and brookite in which anatase was the main phase. Upon increasing the hydrothermal reaction temperature, the degree of crystallinity of the nanoparticles improved and their morphology transformed from bundles of needles to rods and to spheres. Photocatalytic behaviour of the as-synthesized nanoparticles was investigated by photodegradation of methylene blue solution in an ultraviolet A irradiating photoreactor. The as-synthesized nanoparticles exhibited higher photocatalytic performance as compared to the commercial counterpart.
    Matched MeSH terms: Nanoparticles
  17. Fulltext Gold Nanoparticle Conjugation Enhances the Antiacanthamoebic Effects of Chlorhexidine
    Aqeel Y, Siddiqui R, Anwar A, Shah MR, Khan NA
    Antimicrob Agents Chemother, 2015;60(3):1283-8.
    PMID: 26666949 DOI: 10.1128/AAC.01123-15
    Acanthamoeba keratitis is a serious infection with blinding consequences and often associated with contact lens wear. Early diagnosis, followed by aggressive topical application of drugs, is a prerequisite in successful treatment, but even then prognosis remains poor. Several drugs have shown promise, including chlorhexidine gluconate; however, host cell toxicity at physiologically relevant concentrations remains a challenge. Nanoparticles, subcolloidal structures ranging in size from 10 to 100 nm, are effective drug carriers for enhancing drug potency. The overall aim of the present study was to determine whether conjugation with gold nanoparticles enhances the antiacanthamoebic potential of chlorhexidine. Gold-conjugated chlorhexidine nanoparticles were synthesized. Briefly, gold solution was mixed with chlorhexidine and reduced by adding sodium borohydride, resulting in an intense deep red color, indicative of colloidal gold-conjugated chlorhexidine nanoparticles. The synthesis was confirmed using UV-visible spectrophotometry that shows a plasmon resonance peak of 500 to 550 nm, indicative of gold nanoparticles. Further characterization using matrix-assisted laser desorption ionization-mass spectrometry showed a gold-conjugated chlorhexidine complex at m/z 699 ranging in size from 20 to 100 nm, as determined using atomic force microscopy. To determine the amoebicidal and amoebistatic effects, amoebae were incubated with gold-conjugated chlorhexidine nanoparticles. For controls, amoebae also were incubated with gold and silver nanoparticles alone, chlorhexidine alone, neomycin-conjugated nanoparticles, and neomycin alone. The findings showed that gold-conjugated chlorhexidine nanoparticles exhibited significant amoebicidal and amoebistatic effects at 5 μM. Amoebicidal effects were observed by parasite viability testing using a Trypan blue exclusion assay and flow-cytometric analysis using propidium iodide, while amoebistatic effects were observed using growth assays. In contrast, chlorhexidine alone, at a similar concentration, showed limited effects. Notably, neomycin alone or conjugated with nanoparticles did not show amoebicidal or amoebistatic effects. Pretreatment of A. castellanii with gold-conjugated chlorhexidine nanoparticles reduced amoeba-mediated host cell cytotoxicity from 90% to 40% at 5 μM. In contrast, chlorhexidine alone, at similar concentrations, had no protective effects for the host cells. Similarly, amoebae treated with neomycin alone or neomycin-conjugated nanoparticles showed no protective effects. Overall, these findings suggest that gold-conjugated chlorhexidine nanoparticles hold promise in the improved treatment of A. castellanii keratitis.
    Matched MeSH terms: Metal Nanoparticles
  18. Fulltext A selective ultrahigh responding high temperature ethanol sensor using TiO2 nanoparticles
    Arafat MM, Haseeb AS, Akbar SA
    Sensors (Basel), 2014;14(8):13613-27.
    PMID: 25072346 DOI: 10.3390/s140813613
    In this research work, the sensitivity of TiO2 nanoparticles towards C2H5OH, H2 and CH4 gases was investigated. The morphology and phase content of the particles was preserved during sensing tests by prior heat treatment of the samples at temperatures as high as 750 °C and 1000 °C. Field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM) and X-ray diffraction (XRD) analysis were employed to characterize the size, morphology and phase content of the particles. For sensor fabrication, a film of TiO2 was printed on a Au interdigitated alumina substrate. The sensing temperature was varied from 450 °C to 650 °C with varying concentrations of target gases. Results show that the sensor has ultrahigh response towards ethanol (C2H5OH) compared to hydrogen (H2) and methane (CH4). The optimum sensing temperature was found to be 600 °C. The response and recovery times of the sensor are 3 min and 15 min, respectively, for 20 ppm C2H5OH at the optimum operating temperature of 600 °C. It is proposed that the catalytic action of TiO2 with C2H5OH is the reason for the ultrahigh response of the sensor.
    Matched MeSH terms: Nanoparticles/chemistry*
  19. Fulltext Optimization of Quercetin loaded Palm Oil Ester Based Nanoemulsion Formulation for Pulmonary Delivery
    Arbain NH, Salim N, Wui WT, Basri M, Rahman MBA
    J Oleo Sci, 2018 Aug 01;67(8):933-940.
    PMID: 30012897 DOI: 10.5650/jos.ess17253
    In this research, the palm oil ester (POE)- based nanoemulsion formulation containing quercetin for pulmonary delivery was developed. The nanoemulsion formulation was prepared by high energy emulsification method and then further optimized using D-optimal mixture design. The concentration effects of the mixture of POE:ricinoleic acid (RC), ratio 1:1 (1.50-4.50 wt.%), lecithin (1.50-2.50 wt.%), Tween 80 (0.50-1.00 wt.%), glycerol (1.50-3.00 wt.%), and water (88.0-94.9 wt.%) towards the droplet size were investigated. The results showed that the optimum formulation with 1.50 wt.% POE:RC, 1.50 wt.% lecithin, 1.50 wt.% Tween 80, 1.50 wt.% glycerol and 93.90 % water was obtained. The droplet size, polydispersity index (PDI) and zeta potential of the optimized formulation were 110.3 nm, 0.290 and －37.7 mV, respectively. The formulation also exhibited good stability against storage at 4℃ for 90 days. In vitro aerosols delivery evaluation showed that the aerosols output, aerosols rate and median mass aerodynamic diameter of the optimized nanoemulsion were 99.31%, 0.19 g/min and 4.25 µm, respectively. The characterization of physical properties and efficiency for aerosols delivery results suggest that POE- based nanoemulsion containing quercetin has the potential to be used for pulmonary delivery specifically for lung cancer treatment.
    Matched MeSH terms: Nanoparticles
  20. In vitro evaluation of the inhalable quercetin loaded nanoemulsion for pulmonary delivery
    Arbain NH, Salim N, Masoumi HRF, Wong TW, Basri M, Abdul Rahman MB
    Drug Deliv Transl Res, 2019 04;9(2):497-507.
    PMID: 29541999 DOI: 10.1007/s13346-018-0509-5
    Bioavailability of quercetin, a flavonoid potentially known to combat cancer, is challenging due to hydrophobic nature. Oil-in-water (O/W) nanoemulsion system could be used as nanocarrier for quercertin to be delivered to lung via pulmonary delivery. The novelty of this nanoformulation was introduced by using palm oil ester/ricinoleic acid as oil phase which formed spherical shape nanoemulsion as measured by transmission electron microscopy and Zetasizer analyses. High energy emulsification method and D-optimal mixture design were used to optimize the composition towards the volume median diameter. The droplet size, polydispersity index, and zeta potential of the optimized formulation were 131.4 nm, 0.257, and 51.1 mV, respectively. The formulation exhibited high drug entrapment efficiency and good stability against phase separation and storage at temperature 4 °C for 3 months. It was discovered that the system had an acceptable median mass aerodynamic diameter (3.09 ± 0.05 μm) and geometric standard deviation (1.77 ± 0.03) with high fine particle fraction (90.52 ± 0.10%), percent dispersed (83.12 ± 1.29%), and percent inhaled (81.26 ± 1.28%) for deposition in deep lung. The in vitro release study demonstrated that the sustained release pattern of quercetin from naneomulsion formulation up to 48 h of about 26.75% release and it was in adherence to Korsmeyer's Peppas mechanism. The cytotoxicity study demonstrated that the optimized nanoemulsion can potentially induce cyctotoxicity towards A549 lung cancer cells without affecting the normal cells. These results of the study suggest that nanoemulsion is a potential carrier system for pulmonary delivery of molecules with low water solubility like quercetin.
    Matched MeSH terms: Nanoparticles/administration & dosage*; Nanoparticles/chemistry
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