Determination and characterization of metronidazole–kaolin interaction

AbstractThe needs for safe, therapeutically effective antidiarrheal combination continuously lead to effective treatment. When administered simultaneously, metronidazole–kaolin interactions have been reported by FDA but not studied. This paper is the first to study metronidazole–kaolin interactions. Adsorption isotherms of a metronidazole–kaolin antidiarrheal combination from aqueous solutions at an in vivo simulated pH conditions were obtained at 37±0.5°C. Langmuir constants for the adsorption are 10.8225, 41.3223mgg−1 and 11.60, 2.56lg−1 aimed at the monolayer capacity, and the equilibrium constant at pH 1.2 and 6.8, respectively. pH effect on adsorption of known concentration of metronidazole by kaolin was also studied over the range 1.2–8. A gradual increase in the adsorbed amount was noted with increasing the pH. Elution studies by different eluents showed that drug recovery from adsorbent surface was pH-dependent via competitive mechanism. The elution followed the sequence: 0.1M HCl>0.1M NaCl>H2O. Adsorption–desorption studies revealed physical adsorption. The equilibrium concentration of metronidazole decreased as the adsorbent concentration was increased in the systems.The dissolution profiles (USP) of commercially available tablets (Riazole® 500mg) were obtained alone and in the presence of either (ORS®) rehydration salts and 9 or 18g of kaolin powder. The percentage drug released versus time: 95.01% in 25min, 101.02% in 30min, 67.63% in 60min, 60.59% in 60min, respectively.The percentage drug released versus time was increased with ORS® due to common ion effect [Cl−], while, it was decreased with kaolin due to adsorption. The mechanism of reaction of Riazole® (500mg) tablets in the different dissolution media, confirms with Korsmeyer–Peppas model.The interaction between metronidazole and kaolin was characterized by melting point determinations, differential scanning calorimetry analysis and infrared spectroscopy. The results obtained were suggestive of physical interaction between metronidazole and kaolin

Influence of the minimum inhibitory concentration of daptomycin on the outcomes of Staphylococcus aureus bacteraemia

Objectives: Recent studies have shown that methicillin-resistantStaphylococcus aureus (MRSA) bacteraemia with vancomycin minimum inhibitory concentration (MIC) >1 μg/mL is associated with a higher rate of treatment failure and a higher mortality rate. Daptomycin is an alternative to vancomycin but has not been as well studied. The aim of this literature review was to evaluate the effect of daptomycin MIC on the outcomes of S. aureus bacteraemia. Methods: We conducted a literature search for the period January 2010 to January 2019 using the MEDLINE and Embase databases. Results: Four studies were included in the review. The outcomes were clinical cure and 30- or 60-day mortality. In two retrospective studies, 60–70% ofS. aureus isolates had a low daptomycin MIC (≤0.5 μg/mL) and patients with MRSA bacteraemia who were treated with daptomycin had a lower mortality rate. In another study, patients with methicillin-susceptible S. aureus bacteraemia with low daptomycin MICs had a lower risk of developing septic thrombophlebitis. One study showed that patients with MRSA bacteraemia had a higher mortality rate if the daptomycin MIC was >0.5 μg/mL. Conclusion: The included studies in this review suggest a possible association between high daptomycin MIC and unfavourable clinical outcomes ofS. aureus bacteraemia. Further prospective studies are required to evaluate the impact of the daptomycin MIC on the clinical outcomes of S. aureus bacteraemia

EVALUATION OF DIFFERENT GRADES OF GUAR GUM, ACACIA GUM, AND POLYVINYL PYRROLIDONE AS CROSS-LINKERS IN PRODUCING SUBMICRON PARTICLES

Objective: The main goal of this research is to evaluate using of guar gum (GG), Arabic gum, and poly-vinylpyrrolidone, each of two viscosity grades, as crosslinking agents in producing nanoparticles and submicron particles. Methods: The method used is the preparation of nanoparticles of carbamazepine using two viscosity grades of polymers (GG, acacia gum, and polyvinyl pyrrolidine) by emulsification/solvent evaporation technique. Based on a statistical design composed of mixed 32-levels factors and 13-levels factor was selected for screening and preliminary optimization purposes. The collected nanoparticles from the first portion of all 24 runs were subjected to the following qualifications, particle diameter, polydispersity index (PDI%), zeta potential, entrapment efficiency (EE%), and drug loading. Results: The study revealed that based on the obtained findings and the associated statistical analysis, influences of stirring rate, polymer type, polymer grade, and polymer loading in different formulation runs resulted in produced particles with different characteristics such as particle size of different formulation series are in sub-micron (0.13–91.83 μm) with EE% (max 52.28%), reduced EE observed in this study can be attributed to lower polymer load in the dispersed phase (1% and 10%) and zeta potential values were small (range 35.69–41.68), all preparation factors have no significant effect on zeta potential, PDI values (close to zero) showed that all the samples formed monodispersions in water and its due to steric hindrance than a surface charge. Conclusion: The study recommends that different polymers need special techniques for producing cross-linked particles with sub-micron particles, no universal technique can be applied. Keywords: Polymer, Guar gum, Acacia gum, Polyvinyl pyrrolidine, Carbamazepine, Emulsification/solvent evaporation technique, Stirring rate

Evaluation of the Clinical Outcome and Cost Analysis of Antibiotics in the Treatment of Acute Respiratory Tract Infections in the Emergency Department in Saudi Arabia

This study aims to assess the prevalence and antibiotic-treatment patterns of respiratory tract infections (RTIs), prevalence and types of antibiotic-prescribing errors, and the cost of inappropriate antibiotic use among emergency department (ED) patients. A cross-sectional study was conducted at the ED in King Abdulaziz Medical City, Riyadh, Saudi Arabia. Patient characteristics (age, sex, weight, allergies, diagnostic tests (CX-Ray), cultures, microorganism types, and prescription characteristics) were studied. During the study, 3185 cases were diagnosed with RTIs: adults (>15 years) 55% and pediatrics (<15 years) 44%. The overall prevalence of RTIs was 21%, differentiated by upper respiratory tract infections (URTI) and lower respiratory tract infections (LRTI) (URTI 13.4%; LRTI 8.4%), of total visits. Three main antibiotics (ATB) categories were prescribed in both age groups: penicillin (pediatrics 43%; adults 26%), cephalosporin (pediatrics 29%; adults 19%), and macrolide (pediatrics 26%; adults 38%). The prevalence of inappropriate ATB prescriptions was 53% (pediatrics 35%; adults 67%). Errors in ATB included selection (3.3%), dosage (22%), frequency (3%), and duration (32%). There is a compelling need to create antimicrobial stewardship (AMS) programs to improve antibiotic use due to the high number of prescriptions in the ED deemed as inappropriate. This will help to prevent unwanted consequences on the patients and the community associated with antibiotic use

Preparation and characterization of Meta-bromo-thiolactone calcium alginate nanoparticles

Recently, the focus has been shifting toward Quorum sensing inhibitors which reduce Pseudomonas aeruginosa virulence factors, alleviating infections. In this work, me-ta-bromo-thiolactone (mBTL), a potent quorum and virulence inhibitor for the Pseudomonas aeruginosa strains, were formulated in calcium alginate nanoparticles (CANPs). Alginate is used as nutrients and as backbone virulence aspect for Pseudomonas and therefore was chosen. mBTL-loaded-CANPs were characterized for particle size, polydispersity index, zeta potential, morphology visualized by Transmission Electron Microscopy (TEM) and drug release profile. Chemical and physical analysis of formulated mBTL-loaded-CANPs were evaluated using Fourier transform infrared Spectroscopy (FTIR) and differential scanning calorimetry (DSC) and Physical stability of mBTL-loaded-CANPs assessed at various temperature 25 ± 1 °C, 4 ± 0.5 °C and −30° ± 1 °C over a period of 4 and 9 months. Synthesized CANPs showed nano-size particles ranging from 140 to 200 nm with spherical particles for plain CANPS and irregular shape for mBTL-loaded-CANPs with a sustainable release profile over 48hrs. FTIR showed stable structure of loaded-mBTL and DSC displayed no interaction between mBTL and polymer. State of released mBTL from CANPs kept at 25 °C, 4 °C and −30 °C over 4 and 9 months showed stable formula at room temperature which kept as a goal of nanoparticles storage. The findings of this study revealed successful preparation of mBTL-loaded-CANPs

Detection of some haemorrhagic fever viruses in wild shrews collected from different habitats in Saudi Arabia : first record in the Middle East

Shrews (family Soricidae) are tiny mole-shaped mammals belong to the order Eulipotyphla. The main objective of this study is to screen wild specimens of shrews for specific RNA viruses cause hemorrhagic fevers. Wild specimens of shrews were collected from rural areas in Kingdom of Saudi Arabia. Collection of shrews were carried out from the traps then identified using the classical morphological keys. Specimens were dissected then extraction of single stranded RNA of shrews was performed from internal organs including lungs, livers, kidneys, and stomach using QiagenRNeasy Mini Kit. RT-PCR was utilized for screening of Crimean- Congo hemorrhagic fever virus (CCHFV), Rift Valley Fever Virus (RVFV), and Chikengunya virus (CHIKV), and Sindbis virus (SINV). The results revealed SINV, CHIKV, and CCHFV were all found in the internal viscera of shrews in four different groups. This demonstrated that the viruses were propagating and spreading throughout the tissues of the shrews. Conclusions: Depending to our knowledge results of this study constitute first record in Kingdom Saudi Arabia and significantly highlight some of the neglected wild reservoirs of arboviruses; therefore future studies should focus on evaluating other hosts, including bats.Correction in: Journal of King Saud University Science, Volume 34, Issue 3, Article Number 101862, DOI 10.1016/j.jksus.2022.101862</p

Attenuation of Pseudomonas aeruginosa Quorum Sensing Virulence of Biofilm and Pyocyanin by mBTL-Loaded Calcium Alginate Nanoparticles

Pseudomonas aeruginosa contributes to many chronic infections and has been found to be resistant to multiple antibiotics. Pseudomonas use a quorum sensing system (QS) to control biofilm establishment and virulence factors, and, thus, quorum sensing inhibitors (QSIs), such as meta-bromo-thiolactone (mBTL), are promising anti-infective agents. Accordingly, this study intended to investigate the antibacterial and anti-virulence activity of mBTL-loaded calcium alginate nanoparticles (CANPs) against Pseudomonas aeruginosa and different QS mutants. The results show that the mBTL-CANPs had higher antibacterial activity, which was made evident by decreases in all tested strains except the &#8710;lasR/&#8710;rhlR double mutant, with MIC50 (0.5 mg/mL) of mBTL-CANPs compared with free mBTL at MIC50 (&#707;1 mg/mL). The biofilm formation of P. aeruginosa and some QS-deficient mutants were reduced in response to 0.5&ndash;0.125 mg/mL of mBTL-encapsulating CANPs. The pyocyanin production of the tested strains except &#8710;lasA and &#8710;rhlR decreased when challenged with 0.5 mg/mL of mBTL-loaded NPs. The subsequent characterization of the cytotoxic effect of these NPs on human lung epithelial cells (A549) and cystic fibrosis fibroblast cells (LL 29) demonstrated that synthesized NPs were cytocompatible at MIC50 in both cell lines and markedly reduced the cytotoxic effect observed with mBTL alone on these cells. The resulting formulation reduced the P. aeruginosa strains&rsquo; adhesion to A549 comparably with mBTL, suggesting their potential anti-adhesive effect. Given the virulence suppressing action, cytocompatibility, and enhanced anti-biofilm effect of mBTL-CANPs, and the advantage of alginate-based NPs as an antimicrobial delivery system these nanoparticles have great potential in the prophylaxis and treatment of infection caused by Pseudomonas aeruginosa

Measurement and evaluation of the effects of pH gradients on the antimicrobial and antivirulence activities of chitosan nanoparticles in Pseudomonas aeruginosa

Objective: The purpose of this study was to study the antimicrobial activity of chitosan nanoparticles (CSNPs) on Pseudomonas aeruginosa with special emphasis on their sensitivity to pH and the effect of pH on their activity. Methodology: Antimicrobial activity of CSNPs against Pseudomonas aeruginosa at different pH was tested using broth dilution method. Further assessment of antivirulence activity and sensitization of CSNPs on Pseudomonas aeruginosa were examined. Results: Significant antimicrobial effects of CSNPs against Pseudomonas aeruginosa were detected at slightly acidic pH 5, whereas the activity was abolished at a pH of greater than 7. The antivirulence activity of CSNPs was then investigated and treatment with CSNPs (1000 ppm) resulted in a significant reduction or even complete inhibition of pyocyanin production by P. aeruginosa compared with untreated P. aeruginosa indicating the antivirulence activity of CSNPs. CSNPs also sensitized P. aeruginosa to the lytic effects of sodium dodecyl sulfate (SDS); such sensitization was not blocked by washing chitosan-treated cells prior to SDS exposure revealing that CSNPs disturb the outer membrane leading to irreversible sensitivity to detergent even at low concentration (100 ppm). Conclusions: These findings highlight CSNPs as potentially useful as indirect antimicrobial agents for a variety of applications. Keywords: Chitosan nanoparticles, Pseudomonas aeruginosa, pH, Antimicrobial, Virulenc

MicroRNA-539-5p-Loaded PLGA Nanoparticles Grafted with iRGD as a Targeting Treatment for Choroidal Neovascularization

Choroidal neovascularization (CNV) is a major cause of visual impairment that results from excessive growth of blood vessels in the eye’s choroid. The limited clinical efficacy of the current therapy for this condition requires the emergence of new treatment modalities such as microRNA (miRNAs). A recent study identified microRNA-539-5p (miR-539) as an angiogenic suppressor in a CNV animal model; however, its therapeutic delivery is limited. Therefore, this study aims to formulate miR-539 in targeted nanoparticles (NPs) prepared from polylactic-co-glycolic acid (PLGA). The NPs were decorated with internalizing arginylglycylaspartic (RGD) peptide (iRGD), which specifically targets the alpha-v-beta-3 (αvβ3) integrin receptor that is overexpressed in blood vessels of ocular tissue in CNV patients. The 1H NMR spectra results revealed successful conjugation of iRGD peptide into PLGA NPs. The miR-539-PLGA.NPs and miR-539-iRGD-PLGA.NPs were prepared and showed a particle size of 300 ± 3 and 306.40 ± 4 nm, respectively. A reduction in human retinal microvascular endothelial cell (HRMEC) viability was shown 48 and 72 h post transfection with miR-539 incorporated in PLGA NPs and iRGD-PLGA.NPs. iRGD-functionalized PLGA NPs caused further significant reduction in cell viability when compared with plain ones, revealing an enhancement in the NP uptake with iRGD-grafted NPs. The current study showed that miR-539-PLGA.NPs and miR-539-iRGD-PLGA.NPs are promising approaches that reduced the viability of HRMECs, suggesting their therapeutic potential in the treatment of CNV