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Bacterial vaginosis (BV) is a recurring, chronic infection that is difficult to treat due to the limited bioavailability of antimicrobials within vaginal epithelial cells. Vaginal administration, because of lower dosing and systemic exposure offers a viable option for treating vaginal infections. In this study, Metronidazole-loaded chitosan nanoparticles were synthesised employing borax (BX) or tannic acid (TA) as an antimicrobial crosslinking agent for treating BV. The prepared NPs were characterized for various physical, physicochemical, pharmaceutical, thermal and antibacterial properties. Morphological investigation revealed that nanoparticles prepared from 0.5 % w/v chitosan, 1.2 % w/v BX, and 0.4 % w/v metronidazole (MTZ) were non-spherical, with particle sizes of 377.4 ± 37.3 nm and a zeta potential of 34 ± 2.1 mV. The optimised formulation has MIC values of 24 ± 0.5 and 59 ± 0.5 µg/mL, against Escherichia coli (E.coli) and Candida albicans (C.albicans) respectively. The results of DSC and XRD demonstrated no change in the physical state of the drug in the finished formulation. Under simulated vaginal fluid, the optimised formulation demonstrates a cumulative drug release of about 90 % within 6h. The prepared borax crosslinked NPs exhibit anti-fungal activities by inhibiting ergosterol synthesis. The in-vivo antibacterial data indicated a comparable reduction in bacterial count compared to the marketed formulation in female Swiss albino mice treated with optimised nanoparticles. According to histopathological findings, the prepared nanoparticle was safe for vaginal use. Based on the experimental findings, it was concluded that MBCSNPs, due to their good physiochemical and antimicrobial properties, could serve as a potential topical alternative for treating BV and reducing fungal infection.
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Quitosana , Nanopartículas , Vaginose Bacteriana , Feminino , Humanos , Animais , Camundongos , Metronidazol/farmacologia , Vaginose Bacteriana/tratamento farmacológico , Quitosana/química , Portadores de Fármacos/química , Antibacterianos/química , Nanopartículas/química , Tamanho da PartículaRESUMO
In recent times, there has been a notable surge in the investigation of new antibiotic substances derived from natural origins. Pleurotus eous is an edible mushroom that has various useful bioactive substances and therapeutic properties, including antimicrobial activity. The present study aims to evaluate the antimicrobial efficacy of the methanolic extract of P. eous (MEPE) through in vitro method. Notably, S. aureus demonstrated the highest susceptibility to MEPE, prompting further investigation into its antibacterial mechanisms via scanning electron microscopy (SEM), membrane integrity, and permeability assays. The in-vivo antibacterial effect of MEPE against S. aureus was also assessed, including analysis of bacterial burden in organs, hematological profiles, and cytokine profiles. Detailed phytochemical analyses of MEPE were conducted using GC-MS. Results revealed MEPE's significant (p < 0.05) efficacy against Gram-positive bacteria, particularly S. aureus (77.56 ± 0.4 µg/mL and 34 ± 6.9 µg/ml in turbidometric and viable cell count assays, respectively). Moreover, membrane permeability significantly increased in 60.32 % of S. aureus isolates following treatment with MEPE. Additionally, mice receiving MEPE exhibited decreased levels of TNF-α, IL-1ß, and IL-6, suggesting its potential in combating S. aureus infection in animal models.
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Antibacterianos , Testes de Sensibilidade Microbiana , Pleurotus , Staphylococcus aureus , Fator de Necrose Tumoral alfa , Pleurotus/química , Animais , Camundongos , Staphylococcus aureus/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Fator de Necrose Tumoral alfa/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Microscopia Eletrônica de Varredura , Modelos Animais de Doenças , Bactérias Gram-Positivas/efeitos dos fármacos , Citocinas/metabolismo , Permeabilidade da Membrana Celular/efeitos dos fármacos , Carga Bacteriana/efeitos dos fármacos , Anti-Infecciosos/farmacologia , Anti-Infecciosos/química , Cromatografia Gasosa-Espectrometria de MassasRESUMO
Cervical cancer (CC) is the fourth leading cancer type in females globally. Being an ailment of the birth canal, primitive treatment strategies, including surgery, radiation, or laser therapy, bring along the risk of infertility, neonate mortality, premature parturition, etc. Systemic chemotherapy led to systemic toxicity. Therefore, delivering a smaller cargo of therapeutics to the local site is more beneficial in terms of efficacy as well as safety. Due to the regeneration of cervicovaginal mucus, conventional dosage forms come with the limitations of leaking, the requirement of repeated administration, and compromised vaginal retention. Therefore, these days novel strategies are being investigated with the ability to combat the limitations of conventional formulations. Novel carriers can be engineered to manipulate bioadhesive properties and sustained release patterns can be obtained thus leading to the maintenance of actives at therapeutic level locally for a longer period. Other than the purpose of CC treatment, these delivery systems also have been designed as postoperative care where a certain dose of antitumor agent will be maintained in the cervix postsurgical removal of the tumor. Herein, the most explored localized delivery systems for the treatment of CC, namely, nanofibers, nanoparticles, in situ gel, liposome, and hydrogel, have been discussed in detail. These carriers have exceptional properties that have been further modified with the aid of a wide range of polymers in order to serve the required purpose of therapeutic effect, safety, and stability. Further, the safety of these delivery systems toward vital organs has also been discussed.
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Antineoplásicos , Nanopartículas , Neoplasias do Colo do Útero , Feminino , Recém-Nascido , Humanos , Neoplasias do Colo do Útero/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Lipossomos , HidrogéisRESUMO
The intricate process of protein binding orchestrates crucial drug interactions within the bloodstream, facilitating the formation of soluble complexes. This research endeavours to improve the dissolution and oral bioavailability of Rifampicin (RMP) by strategically manipulating drug-protein binding dynamics and the hydrophobic characteristics of human serum albumin (HSA). Various precipitation techniques leveraging methanol, ammonium sulfate, and heat treatment were meticulously employed to tailor the properties of colloidal albumin (HSA NPs). The resultant complexes underwent comprehensive characterization encompassing evaluations of hydrophobicity, size distribution, surface charge, and structural analyses through FTIR, TG-DSC, XRD, and morphological examinations. The findings revealed a significant binding affinity of 78.07 ± 6.6% with native albumin, aligning with prior research. Notably, the complex RMP-HSA NPs-M13, synthesized via the methanolic precipitation method, exhibited the most substantial complexation, achieving a remarkable 3.5-fold increase, followed by the ammonium sulfate (twofold) and heat treatment (1.07-fold) methods in comparison to native albumin binding. The gastric simulated media exhibited accelerated drug release kinetics, with maximal dissolution achieved within two hours, contrasting with the prolonged release observed under intestinal pH conditions. These findings translated into significant improvements in drug permeation, as evidenced by pharmacokinetic profiles demonstrating elevated Cmax, AUC, t1/2, and MRT values for RMP-HSA NPs-M13 compared to free RMP. In summary, this innovative approach underscores the potential of precipitation methods in engineering stable colloidal carrier systems tailored to enhance the oral bioavailability of poorly soluble drugs, offering a pragmatic and scalable alternative to conventional surfactants, polymers, or high-energy methods for complex formation and production.
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Disponibilidade Biológica , Liberação Controlada de Fármacos , Rifampina , Solubilidade , Rifampina/farmacocinética , Rifampina/química , Rifampina/administração & dosagem , Administração Oral , Animais , Humanos , Precipitação Química , Interações Hidrofóbicas e Hidrofílicas , Albumina Sérica Humana/química , Nanopartículas/química , Ratos , Ligação Proteica , Masculino , Sulfato de Amônio/químicaRESUMO
The primary factor underlying the virulence of Candida albicans is its capacity to form biofilms, which in turn leads to recurrent complications. Over-the-counter antifungal treatments have proven ineffective in eliminating fungal biofilms and the inflammatory cytokines produced during fungal infections. Chitosan nanoparticles offer broad and versatile therapeutic potential as both antifungal agents and carriers for antifungal drugs to combat biofilm-associated Candida infections. In our study, we endeavoured to develop chitosan nanoparticles utilising chitosan and the antifungal crosslinker phytic acid targeting C. albicans. Phytic acid, known for its potent antifungal and anti-inflammatory properties, efficiently crosslinks with chitosan. The nanoparticles were synthesised using the ionic gelation technique and subjected to analyses including Fourier transform infrared spectroscopy, dynamic light scattering, and zeta potential analysis. The synthesised nanoparticles exhibited dimensions with a diameter (Dh) of 103 ± 3.9 nm, polydispersity index (PDI) of 0.33, and zeta potential (ZP) of 37 ± 2.5 mV. These nanoparticles demonstrated an antifungal effect with a minimum inhibitory concentration (MIC) of 140 ± 2.2 µg/mL, maintaining cell viability at approximately 90% of the MIC value and reducing cytokine levels. Additionally, the nanoparticles reduced ergosterol content and exhibited a 62% ± 1.2 reduction in biofilm susceptibility, as supported by colony-forming unit (CFU) and XTT assays-furthermore, treatment with nanoparticles reduced exopolysaccharide production and decreased secretion of aspartyl protease by C. albicans. Our findings suggest that the synthesised nanoparticles effectively combat Candida albicans infections. In vivo studies conducted on a mouse model of vaginal candidiasis confirmed the efficacy of the nanoparticles in combating fungal infections in vivo.
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Anti-Inflamatórios não Esteroides , Antifúngicos , Biofilmes , Candida albicans , Candidíase Vulvovaginal , Quitosana , Reagentes de Ligações Cruzadas , Nanopartículas , Ácido Fítico , Biofilmes/efeitos dos fármacos , Ácido Fítico/química , Ácido Fítico/farmacologia , Ácido Fítico/uso terapêutico , Reagentes de Ligações Cruzadas/química , Reagentes de Ligações Cruzadas/farmacologia , Reagentes de Ligações Cruzadas/uso terapêutico , Quitosana/química , Quitosana/farmacologia , Quitosana/uso terapêutico , Nanopartículas/química , Nanopartículas/uso terapêutico , Antifúngicos/química , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/uso terapêutico , Testes de Sensibilidade Microbiana , Citocinas/imunologia , Candida albicans/efeitos dos fármacos , Candida albicans/patogenicidade , Feminino , Animais , Camundongos , Candidíase Vulvovaginal/tratamento farmacológico , Candidíase Vulvovaginal/metabolismo , Vagina/microbiologiaRESUMO
Drug delivery to the buccal mucosa is one of the most convenient ways to treat common mouth problems. Here, we propose a spray-dried re-dispersible mucoadhesive controlled release gargle formulation to improve the efficacy of chlorhexidine. The present investigation portrays an approach to get stable and free-flowing spray-dried porous aggregates of chlorhexidine-loaded sodium alginate nanoparticles. The ionic gelation technique aided with the chlorhexidine's positive surface charge-based crosslinking, followed by spray drying of the nanoparticle's dispersion in the presence of lactose- and leucine-yielded nano-aggregates with good flow properties and with a size range of about 120-350 nm. Provided with the high entrapment efficiency (87%), the particles showed sustained drug release behaviors over a duration of 10 h, where 87% of the released drug got permeated within 12 h. The antimicrobial activity of the prepared formulation was tested on S. aureus, provided with a higher zone of growth inhibition than the marketed formulation. Aided with an appropriate mucoadhesive strength, this product exhibited extended retention of nanoparticles in the throat region, as shown by in vivo imaging results. In conclusion, the technology, provided with high drug retention and extended effect, could be a potential candidate for treating several types of throat infections.
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Clorexidina , Faringe , Staphylococcus aureus , Sistemas de Liberação de Medicamentos/métodos , Preparações de Ação Retardada , Antissépticos Bucais , Tamanho da PartículaRESUMO
In this study, the effect of enzymatic hydrolysis of globulin fraction of C. moschata (CMH), C. lanatus (CLH) and L. siceraria (LSH) on antioxidant capacity, functional properties, structural and micro-structural properties, as well as amino acid compositions were evaluated. All the hydrolysates exhibited significant antioxidant properties. The essential amino acids content in LSH (92.7 mg/g) was higher than CMH (79.9 mg/g) and CLH (70.5 mg/g). Water absorption capacity (5 g/g), heat stability (89%), emulsifying activity index (98.3 m2/g) and emulsifying stability index (45.1 min) were statistically more significant for LSH as compared to CMH and CLH. In addition, LSH had significantly higher FS and FC at pH 3-9. Among all hydrolysates, LSH showed highest solubility (87.3%) as compared to other hydrolysates. The results suggested that enzymatic hydrolysis improve the antioxidant and functional properties. Thus, the globulin hydrolysates might be served as an innovative source with promising nutritive values, good antioxidant and functional properties. Moreover, these could be used in food and pharmaceutical industries for the development of novel functional foods.
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ETHNOPHARMACOLOGICAL RELEVANCE: Glinus oppositifolius (L.) Aug. DC. belongs to the family Molluginaceae, an annual prostrate herb traditionally used to treat inflammations, arthritis, malarial, wounds, fevers, diarrhoea, cancer, stomach discomfort, jaundice, and intestinal parasites. However, the anti-arthritic activity of the aerial part has still not been reported. AIM OF THE STUDY: To investigate the antioxidant and anti-arthritic activity of G. oppositifolius in Complete Freund's Adjuvant (CFA) induced rats. MATERIALS AND METHODS: The dried aerial parts of this plant material were defatted with n-hexane and extracted by methanol using a soxhlet apparatus. The in vitro anti-arthritic activity of methanolic extract of G. oppositifolius (MEGO) was evaluated in protein denaturation, membrane stabilization, and inhibition of proteinase assay at 25, 50, 100, 200, and 400 µg/ml concentrations. Female Wistar rats were immunized sub-dermally into the right hind paw with 0.1 ml of CFA. Rats were administered with MEGO at doses of 200 and 400 mg/kg once daily for fourteen days after arthritis induction. Assessment of arthritis was performed by measuring paw diameter, arthritic index, arthritic score, body weight, organ weight, and hematological and biochemical parameters, followed by the analysis of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), interleukin-1-beta (IL-1ß), cyclooxygenase-2 (COX-2), interleukin 13 (IL-13) and interleukin 10 (IL-10) and histopathological study. In vivo antioxidant effect was investigated in enzymatic assays. The presence of phytoconstituents was analyzed by Gas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS), respectively. In silico molecular docking study of the compounds was carried out against COX-2, IL-1ß, IL-6, and TNF-α using AutoDock 4.2 and BIOVIA-Discovery Studio Visualizer software. RESULTS: MEGO's in vitro anti-arthritic activity showed dose-dependent inhibition of protein denaturation, membrane stabilization, and proteinase inhibition, followed by significant in vivo anti-arthritic activity. The rats treated with MEGO showed tremendous potential in managing arthritis-like symptoms by restoring hematological, biochemical, and histological changes in CFA-induced rats. MEGO (200 and 400 mg/kg) showed a significant alleviation in the levels of hyper expressed inflammatory mediators (TNF-α, IL-1ß, and IL-6) and oxidative stress (SOD, CAT, GSH, and LPO) in CFA-induced rats. Spergulagenin-A as identified by LC-MS analysis, exhibited the highest binding affinity against COX-2 (-8.6), IL-1ß (7.2 kcal/mol), IL-6 (-7.4 kcal/mol), and TNF-α (-6.5 kcal/mol). CONCLUSIONS: Provided with the comprehensive investigation, methanolic extract of G. oppositifolius against arthritic-like condition is a proof of concept that revalidates its ethnic claim. The presence of Spergulagenin-A might be responsible for the anti-arthritic activity.
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Artrite Experimental , Molluginaceae , Ratos , Animais , Fator de Necrose Tumoral alfa , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Interleucina-6 , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Ratos Wistar , Ciclo-Oxigenase 2 , Simulação de Acoplamento Molecular , Quimiometria , Artrite Experimental/induzido quimicamente , Artrite Experimental/tratamento farmacológico , Metanol/química , Antioxidantes/uso terapêutico , Interleucina-13 , Peptídeo Hidrolases , Componentes Aéreos da PlantaRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Tecoma stans (L.) Juss.ex Kunth (Bignoniaceae) is mainly found in tropical and subtropical regions of Africa and Asia. The leaves, flowers, roots, and bark are used to treat various aliments includes, skin infections, kidney problems, intestinal disorders, jaundice, toothaches, joint pain and repair cracked bones, antidotes for snake, scorpion, and rat bites. AIM OF THE STUDY: The objective of the study is to assess the anti-arthritic properties of T. stans leaf using Complete Freund's adjuvant (CFA)-induced rat. MATERIALS AND METHOD: The ethanol extract of T. stans leaf (ETSL) was subjected toGas Chromatography-Mass Spectrometry (GC-MS) and Liquid Chromatography-Mass Spectrometry (LC-MS) analysis for the identification of potential bioactive. The anti-arthritic activity was carried out by administering CFA (0.1 ml) into the sub-plantar surface of the right hind paw. The experimental animals were treated with indomethacin (10 mg/kg) and ETSL (250, 500 mg/kg) once a day orally for fourteen days. The arthritic parameters and hematological and biochemical parameters were evaluated using standard kit reagents. The levels of pro-inflammatory cytokines and inflammatory mediators were measured in blood serum. Antioxidant parameters were assessed in homogenized liver and joint tissues. Radiological and histopathological analysis of joint was performed. A computational molecular docking investigation of the phytoconstituents was conducted against COX-2, IL-1ß, IL-6, and TNF-α receptors. RESULTS: The ETSL at 500 mg/kg demonstrated significant (p < 0.01) restoration of arthritic parameters, hematological and biochemical indices and oxidative stress in CFA-induced rats which was further supported by radiological histological examination. In addition, there was significant (p < 0.05) reduction observed in pro-inflammatory cytokines, inflammatory mediators and up-regulation of anti-inflammatory cytokines in the treated group. Verbascoside was found to exhibit better biding affinities -10.4, -7.4, -7 and -6.2 kcal/mol against COX-2, IL-1ß, TNF-α, and IL-6 respectively, confirmed through in silico study. CONCLUSIONS: The observed outcome suggests that ETSL at a dosage of 500 mg/kg demonstrated notable anti-arthritic effects by suppressing pro-inflammatory cytokines and oxidative stress biomarkers. This effect could potentially be attributed to the presence of bioactive verbascoside identified in the LC-MS analysis.
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Breast cancer is a serious concern for many women worldwide. Drug-loaded implants have shown several benefits over systemic administrations. To provide anti-cancer drugs with controlled release and reduced systemic toxicity, biodegradable in situ implants have attracted a lot of attention. In the present study, we aimed to design and optimize a doxorubicin-loaded chitosan-poloxamer in situ implant for breast cancer treatment. Utilizing Box-Behnken Design and a Quality-by-Design (QbD) methodology, the in situ implant was prepared with chitosan (X1), poloxamer 407 concentration (X2), and stirring time (X3) as the independent variables. It was characterized for its in vitro gelation time, pH, rheology, and morphology, and evaluated based on drug release profile, in vitro cytotoxicity activities, in vitro anti-inflammatory potential, in vitro cellular uptake, and in vivo anti-inflammatory and pharmacokinetics to ensure their therapeutic outcomes. The results revealed that the prepared formulation showed a gelation time of 26 ± 0.2 s with a viscosity of 8312.6 ± 114.2 cPs at 37 °C. The developed formulation showed better cytotoxic activity in MCF-7 cell lines compared to the free drug solution. It demonstrated reduced levels of pro-inflammatory cytokines in RAW 264.7 macrophages. Further, the prepared in situ implant increases the intracellular accumulation of DOX in the MCF-7 cells. The in vivo pharmacokinetic investigations depicted an increase in t 1/2 and a decrease in AUC of the developed formulation resulting in prolonged drug release and there could be a lower drug concentration in the bloodstream than for the free drug. Therefore, the developed in situ implant may offer a viable option for breast cancer treatment.
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INTRODUCTION: Luteolin (LUT), a naturally occurring flavonoid found in vegetables, fruits, and herbal medicines, has been extensively studied for its pharmacological activities, including anti-proliferative and anticancer effects on various cancer lines. It also exhibits potent antioxidant properties and pro-apoptotic activities against human cancers. However, its therapeutic potential is hindered by its poor solubility in water (5 µg/ml at 45°C) and low bioavailability. This research on the development of luteolin-loaded nanocarrier aims to overcome these limitations, thereby opening up new possibilities in cancer treatment. METHODS: This paper covers several nanoformulations studied to increase the solubility and bioavailability of LUT. The physicochemical characteristics of the nanoformulation that influence luteolin's solubility and bioavailability have been the subject of more in-depth investigation. Furthermore, it examines how LUT's anti-inflammatory and antioxidant properties aid in lessening the side effects of chemotherapy. RESULTS: Most nanoformulations, including phytosomes, lipid nanoparticles, liposomes, protein nanoparticles, polymer micelles, nanoemulsions, and metal nanoparticles, have shown promising results in improving the solubility and bioavailability of LUT. This is a significant step forward in enhancing the therapeutic potential of LUT in cancer treatment. Furthermore, the study found that LUT's ability to scavenge free radicals can significantly reduce the side effects of cancer treatment, further highlighting its potential to improve patient outcomes. CONCLUSION: Nanoformulations, because of their unique surface and physiochemical properties, improve the solubility and bioavailability of LUT. However, poor in-vitro and in-vivo correlation and scalability of nanoformulations need to be addressed to achieve good clinical performance of LUT in oncology.
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Antineoplásicos , Portadores de Fármacos , Luteolina , Nanopartículas , Neoplasias , Humanos , Luteolina/farmacologia , Luteolina/química , Luteolina/administração & dosagem , Luteolina/farmacocinética , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Nanopartículas/química , Portadores de Fármacos/química , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/administração & dosagem , Animais , Sistemas de Liberação de Medicamentos , Solubilidade , Disponibilidade BiológicaRESUMO
Design of biocompatible nano-heterostructure photocatalyst with broad UV-visible spectrum response and strong redox ability is a promising approach with potential application in micropollutant degradation and pathogen deactivation from aqueous sources. Herein, we have reported the facile fabrication of In2S3/Bi2Fe4O9 (ISxBFO) binary heterostructure by hydrothermally depositing In2S3 nanoparticles (20-40 nm) over Bi2Fe4O9 nanocuboids/nanoplates prepared by combustion synthesis route. In depth characterization study revealed broad spectrum UV-Vis absorption, large interfacial contact, improved charge carrier separation and mobility and a longer excited state life time (4.7 ns) for the ISxBFO heterostructure materials. The integration of In2S3 with Bi2Fe4O9 strongly boosts the optoelectrical and photocatalytic property of pristine Bi2Fe4O9. The ISxBFO heterostructure material exhibited enhanced photocatalytic efficiency for aqueous phase degradation of sulfamethoxazole antibiotics (kapp = 0.06 min-1) and phenyl urea herbicides (kapp = 0.028 min-1) with reaction rates 3-8 times higher than the pure BFO component. The MTT assay experiments confirmed non-cytotoxic nature of treated sulfamethoxazole and diuron solutions. The composite materials also displayed convincing antibacterial behavior towards toxigenic Vibrio cholerae pathogen. Haemagglutination assay study revealed excellent biocompatibility of the binary composite up to 200 mg L-1. Radical trapping study suggested expeditious generation of â¢OH and â¢O2- radicals over the ISxBFO surface which is nearly 3.8 and 2.3 times higher than pure BFO and In2S3 respectively. The occurrence of a direct Z-scheme mechanism is inferred from radical trapping and XPS study which accounted for the improved photocatalytic activity and strong radical generation property of the ISxBFO heterostructure material.
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Descontaminação , Água , Antibacterianos/química , Antibacterianos/farmacologia , Catálise , SulfametoxazolRESUMO
The emergence of highly virulent CoVs (SARS-CoV-2), the etiologic agent of novel ongoing "COVID-19" pandemics has been marked as an alarming case of pneumonia posing a large global healthcare crisis of unprecedented magnitude. Currently, the COVID-19 outbreak has fueled an international demand in the biomedical field for the mitigation of the fast-spreading illness, all through the urgent deployment of safe, effective, and rational therapeutic strategies along with epidemiological control. Confronted with such contagious respiratory distress, the global population has taken significant steps towards a more robust strategy of containment and quarantine to halt the total number of positive cases but such a strategy can only delay the spread. A substantial number of potential vaccine candidates are undergoing multiple clinical trials to combat COVID-19 disease, includes live-attenuated, inactivated, viral-vectored based, sub-unit vaccines, DNA, mRNA, peptide, adjuvant, plant, and nanoparticle-based vaccines. However, there are no licensed anti-COVID-19 drugs/therapies or vaccines that have proven to work as more effective therapeutic candidates in open-label clinical trial studies. To counteract the infection (SARS-CoV-2), many people are under prolonged treatment of many chemical drugs that inhibit the PLpro activity (Ribavirin), viral proteases (Lopinavir/Ritonavir), RdRp activity (Favipiravir, Remdesivir), viral membrane fusion (Umifenovir, Chloroquine phosphate (CQ), Hydroxychloroquine phosphate (HCQ), IL-6 overexpression (Tocilizumab, Siltuximab, Sarilumab). Mesenchymal Stem Cell therapy and Convalescent Plasma Therapy have emerged as a promising therapeutic strategy against SARS-CoV-2 virion. On the other hand, repurposing previously designed antiviral agents with tolerable safety profile and efficacy could be the only promising approach and fast response to the novel virion. In addition, research institutions and corporations have commenced the redesign of the available therapeutic strategy to manage the global crisis. Herein, we present succinct information on selected anti-COVID-19 therapeutic medications repurposed to combat SARS-CoV-2 infection. Finally, this review will provide exhaustive detail on recent prophylactic strategies and ongoing clinical trials to curb this deadly pandemic, outlining the major therapeutic areas for researchers to step in.
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Cryopreservation and the low revival rate of cryopreserved cells remains a major challenge in cell based bone regeneration therapies. In our current study we aimed to develop a sericin based hydrogel composite incorporating various drugs and growth factors to enhance cell attachment, cryopreservation to increase the cellular viability upon revival. Sericin, gelatin and carrageenan blended hydrogel composites were prepared and explored for their physicochemical properties. The hydrogels prepared were porous and showed higher biocompatibility. Further, silver nanoparticles, alendronate and insulin like growth factor (IGF-1) were incorporated into the hybrid hydrogels individually and checked for sustained drug release profile. IGF-1 incorporated hydrogels composites showed better osteogenic cell attachment, proliferation and cell revival upon cryopreservation. The clonogenic potential of seeded cells upon 30 days of cryopreservation was also evaluated which was 55% in IGF-1 incorporated scaffold cells. A flow cytometry based staining protocol using Annexin V was developed which showed a live cell population up to 80% even after 30 days of crypreservation. These results validate the potential of our formulated hydrogels as cell based systems aimed for increasing cell survival upon cryopreservation and thus has a great potential for bone repair and regeneration.
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Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Carragenina/química , Criopreservação , Gelatina/química , Hidrogéis/química , Sericinas/química , Apoptose/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Teste de MateriaisRESUMO
Cucurbita moschata and Lagenaria siceraria seed proteins were extracted and hydrolysed with trypsin in order to recover antibacterial peptides. Amino acid content and molecular weight distribution were estimated to justify their co-relationship with antimicrobial activity. Antimicrobial activities of C. moschata and L. siceraria seed protein hydrolysates against three Gram-negative bacteria and two Gram-positive bacteria were evaluated. Seed protein hydrolysates of both of these plants have significantly higher activity against Acinetobacter baumannii (p < 0.05). The lethal concentration (LC50) values of L. siceraria hydrolysates (LSH) and C. moschata hydrolysates (CMH) were 70 ± 6.2 and 135.6 ± 4.5 µg/mL in viable count method and 73.2 ± 2.9 and 122.9 ± 3.2 µg/mL in turbidity method, respectively, against A. baumannii. Based on the above findings, seed protein hydrolysates of these plants may be considered as nutritional food and functional antimicrobial agents in food system.
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Aminoácidos/análise , Anti-Infecciosos/análise , Cucurbita/química , Hidrolisados de Proteína/química , Sementes/química , Peptídeos/análise , Extratos Vegetais/químicaRESUMO
The present study is the first effort to a comprehensive evaluation of antityrosinase activity and chemometric analysis of Bauhinia vahlii. The experimental results revealed that the methanol extract of Bauhinia vahlii (BVM) possesses higher polyphenolic compounds and total antioxidant activity than those reported elsewhere for other more conventionally and geographically different varieties. The BVM contain saturated fatty acids such as hexadecanoic acid (10.15%), octadecanoic acid (1.97%), oleic acid (0.61%) and cis-vaccenic acid (2.43%) along with vitamin E (12.71%), α-amyrin (9.84%), methyl salicylate (2.39%) and ß-sitosterol (17.35%), which were mainly responsible for antioxidant as well as tyrosinase inhibitory activity. Tyrosinase inhibitory activity of this extract was comparable to that of Kojic acid. These findings suggested that the B. vahlii leaves could be exploited as potential source of natural antioxidant and tyrosinase inhibitory agent, as well.
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Antioxidantes/farmacologia , Bauhinia/química , Inibidores Enzimáticos/farmacologia , Monofenol Mono-Oxigenase/antagonistas & inibidores , Antioxidantes/química , Avaliação Pré-Clínica de Medicamentos/métodos , Inibidores Enzimáticos/química , Ácidos Graxos/análise , Ácidos Graxos/química , Cromatografia Gasosa-Espectrometria de Massas , Ácido Oleanólico/análogos & derivados , Ácido Oleanólico/análise , Ácidos Oleicos , Extratos Vegetais/química , Folhas de Planta/química , Sitosteroides/análiseRESUMO
In the present study, a modified Osborne fractionation method was followed to isolate albumin (Calb), globulin (Cglo), prolamin (Cpro) and glutelin (Cglu) successively from seeds of Citrullus lanatus (watermelon). This research work was undertaken to investigate the antimicrobial and antioxidant activities of isolated protein fractions of C. lanatus seed. Amino acid composition and molecular weight distribution were determined to establish their relationship with antimicrobial and antioxidant activity. Among all the fractions, Cpro was found to be most effective against A. baumannii followed by Calb and Cglo. The results showed that growth of inhibition of these protein fractions differ significantly from each other (p ≤ 0.05). In view of antioxidant potential, Cglo exhibited strongest antioxidant capacity while Cglu showed weakest antioxidant potential.