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Nanodrugs offer promising alternatives to conventionally used over the counter drugs. Compared to its free form, therapeutic benefits, and gastric tissue safety of naproxen sodium nanoformulation (NpNF) were recently demonstrated. Essential regulatory safety data for this formulation are, however, not available. To address this, male and female BALB/c mice were subjected to acute and 14-day repeated-oral dose assessments. Our data indicate that NpNF was well tolerated up to 2000 mg/kg b.w. A 14-day subacute toxicity testing revealed that the oral administration of low dose (30 mg/kg) NpNF did not produce any adverse effects on blood profile and serum biochemical parameters. Levels of oxidative stress markers and antioxidant enzymes neared normal. Histology of selected tissues also showed no evidence of toxicity. In contrast, a ten-fold increase in NpNF dosage (300 mg/kg), demonstrated, irrespective of gender, mild to moderate toxicity (p < 0.05) in the brain, stomach, and heart tissues, while ROS, LPO, CAT, SOD, POD, and GSH levels remained unaffected in the liver, kidney, spleen, testis, and seminal vesicles. No effect on serum biochemical parameters, overall indicated a no-observed-adverse-effect level (NOAEL) is 300 mg/kg. Further increase in dosage (1000 mg/kg) significantly altered all parameters demonstrating that high dose is toxic.

Asunto(s)

Ratones Endogámicos BALB C , Naproxeno , Pruebas de Toxicidad Aguda , Pruebas de Toxicidad Subaguda , Animales , Femenino , Naproxeno/toxicidad , Naproxeno/administración & dosificación , Masculino , Antiinflamatorios no Esteroideos/toxicidad , Antiinflamatorios no Esteroideos/administración & dosificación , Ratones , Administración Oral , Estrés Oxidativo/efectos de los fármacos , Nanopartículas/toxicidad , Relación Dosis-Respuesta a Droga , Nivel sin Efectos Adversos Observados

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Introduction Acne vulgaris is one of the most common skin problems encountered in the dermatology department. It is a chronic, inflammatory disease of the pilosebaceous unit, clinically presenting with comedones, papules, pustules, nodules, and cysts. With its particularly high prevalence in the younger population, it has significant adverse sequelae on patient's quality of life. At present, due to an enhanced understanding of the pathogenesis of acne, various therapeutic modalities are available. The current management strategies generally follow a systematic treatment escalation based on disease severity and treatment response. However meticulous choice of appropriate anti-acne medicine for the acne type is the key to the management plan. Starting with mild to moderate types of acne as per the Leeds photometric grading scale, the most useful topical agents include topical retinoids, benzoyl peroxide, and topical antibiotics while systemic therapies such as oral antibiotics or isotretinoin are generally reserved for moderate to severe acne treatment. The skin of color (SOC) population is a relatively neglected group concerning the optimum and safe management strategies in different dermatological conditions and acne is no different, where there remains a need for comparing the available topical modalities for appropriate drug selection in the treatment of mild to moderate acne in SOC population. Objective The objective of this study was to compare the efficacy of topical 4% benzoyl peroxide versus topical 0.1% adapalene in the treatment of acne vulgaris in the SOC population. Methods The participants were divided into two groups, groups A and B. A total of 64 patients of both genders, with acne vulgaris (duration > three months) were included in the study. In group A, 32 patients were administered topical 0.1% adapalene whereas, in group B, 32 patients were given topical 4% benzoyl peroxide. Both medicines were applied at night daily. Patients were called for follow-up after 12 weeks. In both groups, the final efficacy evaluation was done using the Global Acne Grading System (GAGS) score after 12 weeks of treatment period. Results In group A, the age ranged from 15 to 40 years with a mean age of 25.781±3.93 years while the duration of complaint was 5.843±1.27 months. GAGS score was 25.281±2.65 and mean BMI was 23.092±3.51 kg/m2. In group B, the mean age was 25.187± 4.06 years, the duration of complaint was 7.375±2.25 months, the GAGS score was 23.906± 2.60 while the mean BMI was 21.485±3.88 kg/m2. Efficacy in group A was noted in 25 (78.1%) patients as compared to 24 (75%) patients in group B (p =0.768). Conclusion The present study showed that the safety and efficacy of 0.1% adapalene the traditional drug 4% benzoyl peroxide in the SOC population was comparable.

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Objectives: To identify age-related plasma extracellular vehicle (EVs) phenotypes in healthy adults. Methods: EV proteomics by high-resolution mass spectrometry to evaluate EV protein stability and discover age-associated EV proteins (n=4 with 4 serial freeze-thaws each); validation by high-resolution flow cytometry and EV cytokine quantification by multiplex ELISA (n=28 healthy donors, aged 18-83 years); quantification of WI-38 fibroblast cell proliferation response to co-culture with PKH67-labeled young and old plasma EVs. The EV samples from these plasma specimens were previously characterized for bilayer structure, intra-vesicle mitochondria and cytokines, and hematopoietic cell-related surface markers. Results: Compared with matched exo-EVs (EV-depleted supernatants), endo-EVs (EV-associated) had higher mean TNF-α and IL-27, lower mean IL-6, IL-11, IFN-γ, and IL-17A/F, and similar mean IL-1ß, IL-21, and IL-22 concentrations. Some endo-EV and exo-EV cytokine concentrations were correlated, including TNF-α, IL-27, IL-6, IL-1ß, and IFN-γ, but not IL-11, IL-17A/F, IL-21 or IL-22. Endo-EV IFN-γ and exo-EV IL-17A/F and IL-21 declined with age. By proteomics and confirmed by flow cytometry, we identified age-associated decline of fibrinogen (FGA, FGB and FGG) in EVs. Age-related EV proteins indicated predominant origins in the liver and innate immune system. WI-38 cells (>95%) internalized similar amounts of young and old plasma EVs, but cells that internalized PKH67-EVs, particularly young EVs, underwent significantly greater cell proliferation. Conclusion: Endo-EV and exo-EV cytokines function as different biomarkers. The observed healthy aging EV phenotype reflected a downregulation of EV fibrinogen subpopulations consistent with the absence of a pro-coagulant and pro-inflammatory condition common with age-related disease.

Asunto(s)

Vesículas Extracelulares , Envejecimiento Saludable , Interleucina-27 , Adulto , Humanos , Interleucina-17/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-27/metabolismo , Interleucina-6/metabolismo , Vesículas Extracelulares/metabolismo , Citocinas/metabolismo , Sistema Inmunológico/metabolismo , Fibrinógeno/metabolismo , Compuestos Orgánicos

RESUMEN

Synovial fluid (SF) extracellular vesicles (EVs) play a pathogenic role in osteoarthritis (OA). However, the surface markers, cell and tissue origins, and effectors of these EVs are largely unknown. We found that SF EVs contained 692 peptides that were positively associated with knee radiographic OA severity; 57.4% of these pathogenic peptides were from 46 proteins of the immune system, predominantly the innate immune system. CSPG4, BGN, NRP1, and CD109 are the major surface markers of pathogenic SF EVs. Genes encoding surface marker CSPG4 and CD109 were highly expressed by chondrocytes from damaged cartilage, while VISG4, MARCO, CD163 and NRP1 were enriched in the synovial immune cells. The frequency of CSPG4+ and VSIG4+ EV subpopulations in OA SF was high. We conclude that pathogenic SF EVs carry knee OA severity-associated proteins and specific surface markers, which could be developed as a new source of diagnostic biomarkers or therapeutic targets in OA.

Asunto(s)

Vesículas Extracelulares , Osteoartritis de la Rodilla , Humanos , Osteoartritis de la Rodilla/metabolismo , Líquido Sinovial/metabolismo , Biomarcadores/metabolismo , Péptidos/metabolismo , Vesículas Extracelulares/metabolismo

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OBJECTIVES: To compare the efficacy of intralesional tranexamic acid and topical 4% hydroquinone in the treatment of melasma. STUDY DESIGN: This comparative prospective study was conducted at the Dermatology Department, Pak Emirates Military Hospital Rawalpindi, Pakistan from October 16, 2018 to April 16, 2019. METHODOLOGY: A total of 290 patients with melasma, 18 to 50 years of age, were included in this study. Patients with a history of discoid lupus erythematosus, pregnancy, lactation, anemia, and oral contraceptives or hormone replacement therapy were excluded from the study. Randomization was 1:1 for groups A and B, i.e., each upcoming patient was included in the next group. This randomization was supervised by another clinician. One hundred forty-five patients were placed in group A (intralesional tranexamic acid), while 145 were enrolled in group B (topical 4% hydroquinone). Follow-up was done at four weekly intervals for 12 weeks. After 12 weeks, the final response was assessed. RESULTS: In group A, the average age was 33.74 ± 6.67 years, while in group B it was 32.08 ± 6.08 years. Among the entire patients, the majority of the patients, 207 (71.38%), were in the age range of 18 to 35 years. Intralesional tranexamic acid was efficacious in 64 (44.14%) patients, while 47 (32.41%) of group B (topical 4% hydroquinone) showed complete improvement (p-value = 0.040). CONCLUSION: This study concluded that using intralesional tranexamic acid is more effective in treating melasma than topical 4% hydroquinone.

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INTRODUCTION: The prevalence of depression is increasing day by day, which predisposes individuals toward significant functional impairment, and increases the risk of suicide and comorbid physical health problems. Body mass index (BMI) and depression are supposed to be associated with each other; however, the effects of depression on body image have not been identified from the perspective of socioeconomic status, which has been considered a major risk factor for the development of depression. Hence, the study was designed to evaluate the prevalence of depression among adults in government schools and to analyze its association with BMI among different socioeconomic statuses. METHODOLOGY: It was a cross-sectional study conducted at two government schools in Shah Faisal colony from September to October 2019. The study participants were girls of age between 11 and 18 years belonging to different socioeconomic statuses, i.e. low, middle, and high. The calculated sample size was 550 which was calculated at 50% proportion of the total population. A self-developed proforma was administered for collecting demographic data, and students' weight and height were noted for calculating BMI. The Patient Health Questionnaire (PHQ) 9 modified depression scale was used to assess the depression among study participants. The chi-square test was applied to check the association between BMI and depression score. The study was approved by the IRB of CPSP Karachi and the reference code ME/HCSM/2019/TWC/G-054 was allotted.  Results: There were 345 (62.7%) participants of age 13-15 years, and most of the participants belonged to middle socioeconomic status, 413 (75%). BMI calculation of study participants showed that 417 (75.8%) scored as underweight and 131 (23.8%) had a normal index. According to the PHQ9 scale, 381 (69.3%) participants were having mild depression and 60 (10.9%) had moderate depression. BMI and depression were not associated significantly with a p-value =0.135. CONCLUSION: The BMI score of study participants seemed to be underweight or normal. The study could not rule out the association of BMI with depression. However, according to the PHQ9 scale score, many participants screened as sufferers of mild to moderate depression, which is alarming, as depression at the age of 11-18 years may predispose young girls to chronic disease and other psychological conditions.

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Copper oxide nanoparticles (CuO NPs) were synthesized through the coprecipitation method and used as nanocarriers for etoricoxib (selective COX-2 inhibitor drug) and montelukast (leukotriene product inhibitor drug) in combination therapy. The CuO NPs, free drugs, and nanoformulations were investigated through UV/Vis spectroscopy, FTIR spectroscopy, XRD, SEM, and DLS. SEM imaging showed agglomerated nanorods of CuO NPs of about 87 nm size. The CE1, CE2, and CE6 nanoformulations were investigated through DLS, and their particle sizes were 271, 258, and 254 nm, respectively. The nanoformulations were evaluated through in vitro anti-inflammatory activity, in vivo anti-inflammatory activity, in vivo analgesic activity, in vivo anti-pyretic activity, and in vivo acute toxicity activity. In vivo activities were performed on albino mice. BSA denaturation was highly inhibited by CE1, CE2, and CE6 as compared to other nanoformulations in the in vitro anti-inflammatory activity. The in vivo bioactivities showed that low doses (5 mg/kg) of nanoformulations were more potent than high doses (10 and 20 mg/kg) of free drugs in the inhibition of pain, fever, and inflammation. Lastly, CE2 was more potent than that of other nanoformulations.

Asunto(s)

Acetatos/síntesis química , Acetatos/farmacología , Cobre/química , Ciclopropanos/síntesis química , Ciclopropanos/farmacología , Etoricoxib/síntesis química , Etoricoxib/farmacología , Nanopartículas del Metal , Quinolinas/síntesis química , Quinolinas/farmacología , Sulfuros/síntesis química , Sulfuros/farmacología , Acetatos/química , Analgésicos/síntesis química , Analgésicos/química , Analgésicos/farmacología , Antiinfecciosos/síntesis química , Antiinfecciosos/química , Antiinfecciosos/farmacología , Antiinflamatorios/síntesis química , Antiinflamatorios/química , Antiinflamatorios/farmacología , Técnicas de Química Sintética , Ciclopropanos/química , Composición de Medicamentos , Etoricoxib/química , Nanopartículas del Metal/química , Nanopartículas del Metal/ultraestructura , Quinolinas/química , Análisis Espectral , Relación Estructura-Actividad , Sulfuros/química

RESUMEN

Inflammatory cells orchestrate tumor niche for the proliferating neoplastic cells, leading to neoangiogenesis, lymphangiogenesis, tumor growth and metastasis. Emergence of severe side effects, multiple drug resistance and associated high cost has rendered conventional chemotherapy less effectual. The aim was to develop a multipurpose, less toxic, more potent and cheaper, oral non-conventional anticancer therapeutic. Cyclooxygenase associated with tumor niche inflammation and proliferative neoplastic cells were targeted synergistically, through anti-inflammatory and anti-proliferative effects of model drug, diclofenac sodium and fluorescent silver nanoparticles (AgNPs), respectively. Drug entrapped AgNPs were surface modified with PVA (for controlling particle size, preferred cellular uptake, evading opsonization and improved dispersion). XRD, FTIR, DSC, TGA, LIBS, particle size and surface plasmon resonance analysis confirmed the efficient drug encapsulation and PVA coating with 62% loading efficiency. In-vitro, the formulation exhibited 1st order release kinetics with sustained and maximal release at slightly acidic conditions (pH 4.5) enabling the potential for passive tumor targeting. Also, nanoparticles showed efficient protein denaturation inhibition potential, hemo-compatibility (<0.8%) and potent anti-cancer activity (P < 0.05) against breast cancer cell line (MCF-7). In-vivo, developed nanoparticles improved pharmacokinetics (2.8 fold increased AUC, 6.9 h t1/2, Cmax = 1.6 ±â€¯0.03 µg/ml, Kel = 0.1) and pharmacodynamics manifested by potent anti-inflammatory, analgesic and anti-pyretic effects (P < 0.05) at 20 fold lower doses. LD50 determination revealed a wide therapeutic window. The study showed promise of synthesized nanomaterials as cheaper, less toxic, hemo-compatible, oral and more potent anti-inflammatory and non-conventional fluorescent anti-cancer agents, vanquishing tumor niche inflammation and repressing proliferation of malignant cells.

Asunto(s)

Antineoplásicos , Nanopartículas del Metal , Nanopartículas , Neoplasias , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Humanos , Células MCF-7 , Tamaño de la Partícula , Plata

RESUMEN

OBJECTIVE: The purpose of this study was to develop novel carbopol-based miltefosine-loaded transfersomal gel (HePCTG) for the treatment of cutaneous leishmaniasis (CL) via efficient targeting of leishmania infected macrophages. METHODS: Miltefosine-loaded transfersomes (HePCT) were prepared by ethanol injection method followed by their incorporation into carbopol gel to form HePCTG. The prepared HePCT were assessed for physicochemical properties including mean particle size, polydispersity index, zeta potential, entrapment efficiency, morphology, and deformability. Similarly, HePCTG was evaluated for physiochemical and rheological attributes. The in vitro release, skin permeation, skin irritation, anti-leishmanial activity, and in vivo efficacy in BALB/c mice against infected macrophages were also performed for HePCT. RESULTS: The optimized HePCT displayed a particle size of 168 nm with entrapment efficiency of 92%. HePCTG showed suitable viscosity, pH, and sustained release of the incorporated drug. Furthermore, HePCT and HePCTG demonstrated higher skin permeation than drug solution. The results of macrophage uptake study indicated improved drug intake by passive diffusion. The lower half maximal inhibitory concentration value, selectivity index and higher 50% cytotoxic concentration  value of HePCT compared to that of HePC solution demonstrated the improved anti-leishmanial efficacy and non-toxicity of the formulation. This was further confirmed by the notable reduction in parasite load and lesion size observed in in vivo anti-leishmanial study. CONCLUSION: It can be stated that the formulated HePCTG can effectively be used for the treatment of CL.

Asunto(s)

Leishmaniasis Cutánea , Resinas Acrílicas , Animales , Leishmaniasis Cutánea/tratamiento farmacológico , Macrófagos , Ratones , Ratones Endogámicos BALB C , Fosforilcolina/análogos & derivados

RESUMEN

Uncontrolled bleeding remains the leading cause of morbidity and mortality across the entire macrocosm. It refers to excessive loss of blood that occurs inside of body, due to unsuccessful platelet plug formation at the injury site. It is not only limited to the battlefield, but remains the second leading cause of death amongst the civilians, as a result of traumatic injury. Startlingly, there are no effective treatments currently available, to cater the issue of internal bleeding, even though early intervention is of utmost significance in minimizing the mortality rates associated with it. The fatal issue of uncontrolled bleeding is ineffectively being dealt with the use of pressure dressings, tourniquet, and surgical procedures. This is not a practical approach in combat arenas or in emergency situations, where the traumatic injury inflicted is deep inside the body, and cannot be addressed externally, by the application of topical dressings. This review focuses on the traditional hemostatic agents that are used to augment the process of hemostasis, such as mineral zeolites, chitosan based products, biologically active agents, anti-fibrinolytics, absorbable agents, and albumin and glutaraldehyde, as well as the micro- and nano-based hemostatic agents such as synthocytes, thromboerythrocytes, thrombosomes, and the synthetic platelets.

Asunto(s)

Hemorragia/tratamiento farmacológico , Hemostáticos/química , Albúminas/química , Animales , Vendajes , Plaquetas/metabolismo , Celulosa/química , Quitosano/química , Colágeno/química , Glutaral/química , Hemostasis , Hemostáticos/farmacología , Humanos , Almidón/química , Zeolitas/química

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The current study was devised to explore the antibacterial activity and underlying mechanism of spinel ferrite nanoparticles (NPs) along with their biocompatibility and wound healing potentials. In this regard, nickel ferrite and zinc/nickel ferrite NPs were synthesized via a modified co-precipitation method and were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM) and energy Energy-dispersive X-ray spectroscopy (EDX). The biocompatibility of the synthesized NPs with human dermal fibroblast (HDF) and red blood cells (RBCs) was assessed. The biocompatible concentrations of the NPs were used to investigate the antimicrobial activity against various pathogenic Gram-negative and Gram-positive bacteria. The mode of bactericidal action was also explored. In vitro scratch assay was performed to evaluate the wound healing potential of NPs. The SEM-EDX analysis showed that the average particles size of nickel ferrite and zinc/nickel ferrite were 49 and 46 nm, respectively, with appropriate elemental composition and homogenous distribution. The XRD pattern showed all the characteristic diffraction peaks of spinel ferrite NPs, which confirmed the synthesis of the pure phase cubic spinel structure. The biocompatible concentration of nickel ferrite and zinc/nickel ferrite NPs was found to be 250 and 125 µg ml-1, respectively. Both the NPs showed inhibition against all the selected strains in the concentration range of 50 to 1000 µg ml-1. Studies on the underlying antimicrobial mechanism revealed damage to the cell membrane, protein leakage, and intracellular reactive oxygen species production. The in vitro scratch assay confirmed the migration and proliferation of fibroblast with artificial wound shrinkage. This study shows that nickel ferrite and zinc/nickel ferrite NPs could be a strong candidate for antibacterial and wound healing nano-drugs.

RESUMEN

The flustering rise in cancer incidence along with treatment anomalies has made cancer the second leading cause of death globally. The total annual economic impact of cancer is pronounced and is increasing. Besides the lack of proper curative therapy, treatment associated adverse effects, drug resistance, and tumor relapse are the instigations behind increased morbidity and mortality. Meanwhile, the survival rate has inclined impressively. In the last few decades, cancer treatment has undergone wide refinements aiming towards cancer prevention, complete tumor regression, subsiding treatment adverse effects, improving patient's life standard and avoiding tumor relapse. Chemotherapy has been successfully extended towards natural, cheaper and bioactive anti-inflammatory agents manifesting potent anticancer activity. Antibody-based cancer therapy has become well established as a vital and effective strategy for treating hematological malignancies as well as solid tumors. Individualized immunotherapy is becoming the forefront of cancer treatment enabling personalized, precise and patient's cancer mutanome specific adjustable regimen. The emergence of anti-neoangiogenesis and cancer stem cell targeting techniques have dropped cancer recurrence significantly. Advancements in hyperthermia and photodynamic therapies along with improvements in cancer vaccination have declined death rate and amplified survival rate convincingly.

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BACKGROUND: Due to the rapid growth in life threatening diseases such as cancer, diabetes, chronic wound and HIV/AIDS along with rise of side effects of the current treatments, world is now focusing to utilize new treatment options. Currently, the development of green nanotechnology field seems as a potential alternate for diseases diagnosis and treatment by preparation of various sizes and shapes of nanomaterials. OBJECTIVE: This review is to present the explored biological sources in synthesis of nanomaterials particularly metal and metal oxides nanoparticles and critical review of the applications of biosynthesized nanoparticles in pharmaceutical and biomedical fields. METHODS: In this review, the various biological sources including bacteria, fungi, algae and plants used in synthesis of nanomaterials and mechanism involved in preparation are elaborated. In addition, biosynthesized nanomaterials applied as drug delivery system for anticancer, antibiotic, antidiabetic agent and functioned as potential diagnostic, antimicrobial, anticancer and wound healing candidates are comprehensively reviewed. RESULTS: The synthesized metal and metal oxides from green protocol proved to have advantages such as being biocompatible, effective and cheap. Furthermore, the green synthesized metal and metal oxide nanoparticles showed to possess prominent physical, chemical and biological properties that can be efficiently utilized for pharmaceutical and biomedical applications. CONCLUSION: The information gathered in this review will provide a baseline for exploring more potential usage of green synthesized metal and metal oxide nanomaterials for various other applications. However, a concrete understanding of the safety of these nanomaterials is still needed to minimize the potential side effects.

Asunto(s)

Nanopartículas del Metal , Preparaciones Farmacéuticas , Humanos , Metales , Nanotecnología , Óxidos

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Current report is paramount contribution via nanotechnology to the existing remedies of health diseases. The lag in application of capped metallic oxide nanoparticles in restorative dentistry exist which is covered by this promising study. The uncapped and chitosan encapsulated ZnO nanoparticles were fabricated by facile co-precipitation method, and characterized using various biophysical strategies including X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), Scanning electron microscopy (SEM), Transmission electron microscopy (TEM) and Energy dispersive x-ray (EDX). ZnO nanoparticles and ZnO-Citosan nanoparticles were estimated to be <30 nm and <25 nm in size on respective basis. Significant in vitro antibacterial, antioxidant, cytotoxic and antidiabetic activity of ZnO nanoparticles has been elucidated that is enhanced by capping with chitosan polymer. 90% cytotoxicity against brine shrimps, 69.6% antidiabetic activity against α-amylase, and noteworthy antioxidation power by chitosan decorated ZnO nanoparticles has been effectively illustrated. Furthermore, the effective secondary caries remediation approach has been established by an amalgamation of ZnO nanoparticles and ZnO-Chitosan nanoparticles into dentine bonding agents. A remarkable reduction in Streptococcus mutans and Lactobacillus acidophillus strains has been observed, in-specific boosted by chitosan capped ZnO nanoparticles reinforced dental adhesive discs. Additionally, augmented mechanical properties, greater resistance to water sorption and solubility, notably high release profile, and slight variation of shear bond strength values have been obtained. In short, the prepared nanoparticles reported are detected to be auspicious theranostic agents for combating wide array of human pathogens in healthcare system.

Asunto(s)

Quitosano , Nanopartículas del Metal , Nanocompuestos , Nanopartículas , Óxido de Zinc , Animales , Antibacterianos/farmacología , Humanos , Nanopartículas del Metal/toxicidad , Microscopía Electrónica de Rastreo , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos X

RESUMEN

BACKGROUND: Nanocarriers endow tremendous benefits to the drug delivery systems depending upon the specific properties of either component. These benefits include, increase in the drug blood retention time, reduced efflux, additional toxicity and targeted delivery. Methotrexate (MTX) is clinically used for cancer treatment. Higher dosage of MTX results in hepatic and renal toxicity. In this study methotrexate silver nanoparticles (Ag-MTX) coated with polyethylene glycol (PEG) are synthesized and characterized. Their anticancer activity and biocompatibility is also evaluated. RESULTS: Ag-MTX nanoparticles are synthesized by chemical reduction method. They are characterized by Ultraviolet-Visible Spectroscopy and Fourier Transform Infrared Spectroscopy. Average size of PEG coated Ag-MTX nanoparticles (PEG-Ag-MTX nanoparticles) is 12nm. These particles exhibited improved anticancer activity against MCF-7 cell line. Hemolytic activity of these particles was significantly less than MTX. CONCLUSION: PEG-Ag-MTX nanoparticles are potential nanocarrier of methotrexate which may offer MTX based cancer treatment with reduced side effects. In-vivo investigations should be carried out to explore them in detail.

Asunto(s)

Antineoplásicos , Portadores de Fármacos , Nanopartículas del Metal , Metotrexato , Polietilenglicoles , Plata , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Supervivencia Celular/efectos de los fármacos , Portadores de Fármacos/administración & dosificación , Portadores de Fármacos/química , Eritrocitos/efectos de los fármacos , Femenino , Hemólisis/efectos de los fármacos , Humanos , Células MCF-7 , Nanopartículas del Metal/administración & dosificación , Nanopartículas del Metal/química , Metotrexato/administración & dosificación , Metotrexato/química , Polietilenglicoles/administración & dosificación , Polietilenglicoles/química , Plata/administración & dosificación , Plata/química

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BACKGROUND: Pseudomonas aeruginosa (P. aeruginosa) is a highly virulent opportunistic pathogen and a leading cause of nosocomial infections. Affected patients are often hospitalized in an intensive care unit, and are immuno-compromised as a result of disease and treatment. Suspected P. aeruginosa require timely, adequate and empirical antibiotic therapy to ensure improved outcomes. The purpose of the study was to find the sensitivity and resistance pattern of P. aeruginosa to various groups of drugs, in clinical isolates collected from two major tertiary care hospitals of Peshawar. METHODS: Different clinical isolate were taken from patients admitted in various wards of Khyber Teaching Hospital and Lady Reading Hospital Peshawar. RESULTS: A total of 258 clinical isolates were positive for P. aeruginosa out of 2058 clinical isolates. Pseudomonas showed high degree of resistance to third generation Cephalosporins (Ceftazidime, and Ceftriaxone) and moderate degree of resistance to Quinolones and Aminoglycosides (Ofloxacin, Ciprofloxacin, Levofloxacin and Amikacin). Low resistance was observed to different combinations (Cefoperazone+Sulbactum, Piperacillin+Tazobactum). Meropenem and Imipenem had negligible resistance. CONCLUSION: There is growing resistance to different classes of antibiotics. Combination drugs are useful approach for empirical treatment in suspected Pseudomonas infection. Imipenem and Meropenem are extremely effective but should be in reserve.

Asunto(s)

Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana , Infecciones por Pseudomonas/microbiología , Pseudomonas aeruginosa/aislamiento & purificación , Adulto , Anciano , Femenino , Humanos , Incidencia , Unidades de Cuidados Intensivos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Pakistán/epidemiología , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/epidemiología , Pseudomonas aeruginosa/efectos de los fármacos

RESUMEN

Patuletin isolated from Tagetespatula was used as a capping and reducing agent to synthesize in one pot gold nanoparticles capped with patuletin. Conjugation of gold with patuletin was confirmed by FT-IR and UV-visible spectroscopy and amount of patuletin conjugated to gold nanoparticles was found to be 63.2% by weight. Particle sizes were measured by atomic force microscopy (AFM) and were found to have a mean diameter of about 45 nm. Patuletin-coated gold nanoparticles were found to be highly fluorescent. To examine their potential as chemical sensors, they were contacted with fourteen different drugs. Of these drugs, only one, piroxicam, was found to quench luminescence. Quenching obeyed Beer's law in a concentration range of 20-260 µM. Important for molecular recognition applications, fluorescence quenching by piroxicam was not affected by pH variation, elevated temperatures, addition of other drugs and addition of blood plasma to the colloidal suspensions.

Asunto(s)

Cromonas/química , Oro/química , Tecnología Química Verde/métodos , Nanopartículas del Metal/química , Piroxicam/análisis , Espectrometría de Fluorescencia/métodos , Antiinflamatorios no Esteroideos/análisis , Antiinflamatorios no Esteroideos/química , Materiales Biocompatibles Revestidos/síntesis química , Excipientes/química , Nanopartículas del Metal/ultraestructura , Tamaño de la Partícula , Piroxicam/química

RESUMEN

BACKGROUND: Conjugated and drug loaded silver nanoparticles are getting an increased attention for various biomedical applications. Nanoconjugates showed significant enhancement in biological activity in comparison to free drug molecules. In this perspective, we report the synthesis of bioactive silver capped with 5-Amino-ß-resorcylic acid hydrochloride dihydrate (AR). The in vitro antimicrobial (antibacterial, antifungal), enzyme inhibition (xanthine oxidase, urease, carbonic anhydrase, α-chymotrypsin, cholinesterase) and antioxidant activities of the developed nanostructures was investigated before and after conjugation to silver metal. RESULTS: The conjugation of AR to silver was confirmed through FTIR, UV-vis and TEM techniques. The amount of AR conjugated with silver was characterized through UV-vis spectroscopy and found to be 9% by weight. The stability of synthesized nanoconjugates against temperature, high salt concentration and pH was found to be good. Nanoconjugates, showed significant synergic enzyme inhibition effect against xanthine and urease enzymes in comparison to standard drugs, pure ligand and silver. CONCLUSIONS: Our synthesized nanoconjugate was found be to efficient selective xanthine and urease inhibitors in comparison to Ag and AR. On a per weight basis, our nanoconjugates required less amount of AR (about 11 times) for inhibition of these enzymes.

Asunto(s)

Antioxidantes/farmacología , Inhibidores Enzimáticos/farmacología , Nanopartículas del Metal/química , Plata/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Antifúngicos/química , Antifúngicos/farmacología , Antioxidantes/química , Anhidrasa Carbónica II/antagonistas & inhibidores , Técnicas de Química Sintética , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/farmacología , Evaluación Preclínica de Medicamentos/métodos , Inhibidores Enzimáticos/química , Concentración de Iones de Hidrógeno , Hidroxibenzoatos/química , Microscopía Electrónica de Transmisión , Plata/química , Espectrofotometría Ultravioleta , Espectroscopía Infrarroja por Transformada de Fourier , Temperatura , Ureasa/antagonistas & inhibidores , Xantina Oxidasa/antagonistas & inhibidores

RESUMEN

BACKGROUND: The conjugation of gold nanoparticles with biocides such as natural products, oligosaccharides, DNA, proteins has attracted great attention of scientists recently. Gold NPs covered with biologically important molecules showed significant enhancement in biological activity in comparison with the activity of the free biocides. However, these reports are not very systematic and do not allow to draw definitive conclusions. We therefore embarked in a systematic study related to the synthesis and characterization of biocidal activities of Au nanoparticles conjugated to a wide variety of synthetic and natural biomolecules. In this specific report, we investigated the activity of a synthetic biocide, 2-4, Dihydroxybenzene carbodithioic acid (DHT). RESULTS: Au nanoparticles (NP) with a mean size of about 20 nm were synthesized and functionalized in one pot with the help of biocide 2,4-Dihydroxybenzene carbodithioic acid (DHT) to reduce HAuCl4 in aqueous solution. Conjugation of DHT with gold was confirmed by FT-IR and the amount of DHT conjugated to the Au nanoparticles was found to be 7% by weight by measuring the concentration of DHT in the supernatant after centrifugation of the Au NPs. To ascertain the potential for in vivo applications, the stability of the suspensions was investigated as a function of pH, temperature and salt concentration. Antibacterial, antifungal, insecticidal and cytotoxic activities of the Au-DHT conjugates were compared with those of pure DHT and of commercially available biocides. In all cases, the biocidal activity of the Au-DHT conjugates was comparable to that of commercial products and of DHT. CONCLUSIONS: Since the DHT concentration in the Au-DHT conjugates was only about 7%, our results indicate that conjugation to the Au NPs boosts the biocidal activity of DHT by about 14 times. The suspensions were found to be stable for several days at temperatures of up to 100°C, salt concentrations up to 4 mol/L and a pH range of 2-13.

Asunto(s)

Antibacterianos/farmacología , Oro/farmacología , Nanopartículas del Metal/química , Viabilidad Microbiana/efectos de los fármacos , Tiocarbamatos/química , Animales , Antibacterianos/química , Artemia/efectos de los fármacos , Bacterias/efectos de los fármacos , Hongos/efectos de los fármacos , Oro/química , Calor , Concentración de Iones de Hidrógeno , Tamaño de la Partícula , Plaguicidas/química , Plaguicidas/farmacología , Cloruro de Sodio

RESUMEN

In the title compound, C(15)H(12)N(2)O(7), the dihedral angle between the aromatic rings is 4.58 (13)° and the nitro group is rotated from its attached ring by 18.07 (17)°. Intra-molecular N-H⋯O and O-H⋯O hydrogen bonds generate S(5) and S(6) rings, respectively. In the crystal, mol-ecules are linked by O-H⋯O hydrogen bonds, generating [001] C(7) chains. The chains are linked by C-H⋯O inter-actions, forming a three-dimensional network, which incorporates R(2) (2)(7) and R(2) (2)(10) loops.