Fabrication of inhaled hybrid silver/ciprofloxacin nanoparticles with synergetic effect against Pseudomonas aeruginosa

Ciprofloxacin (CFX) is a fluroquinolone antibiotic used as a first line treatment against infections caused by Pseudomonas aeruginosa and Streptococcus pneumonia that are commonly acquired by cystic fibrosis (CF) patients. However, no inhalation formulation is currently available for ciprofloxacin. Hybrid silica coated silver nanoparticles were prepared using Stöber reaction and the optimum ratio of chitosan and sodium tripolyphosphate was used to encapsulate CFX. Particle deposition was assessed in vitro using twin stage impinger while antimicrobial activity was evaluated based on the planktonic growth of P. aeruginosa as well as against P. aeruginosa sp biofilm formation. In vitro deposition results showed significant deposition in stage 2 using twin stage impinger (TSI) (∼70%). Compared to CFX, the formed hybrid nanoparticles were 3-4 folds more effective against inhibiting growth and biofilm formation by P. aeruginosa PAO1 and P. aeruginosa NCTC 10662

Fabrication of biopolymer based nanoparticles for the entrapment of chromium and iron supplements

The objective of this study was to encapsulate iron and chromium into novel nanoparticles formulated using chitosan (CS), dextran sulfate (DS) and whey protein isolate (WPI) for oral drug delivery. Empty and loaded CS-DS nanoparticles were prepared via complex coacervation whilst whey protein nanocarriers were produced by a modified thermal processing method using chitosan. The physiochemical properties of the particles were characterized to determine the effects of formulation variables, including biopolymer ratio on particle size and zeta potential. Permeability studies were also undertaken on the most stable whey protein–iron nanoparticles by measuring Caco-2 ferritin formation. A particle size analysis revealed that the majority of samples were sub-micron sized, ranging from 420–2400 nm for CS-DS particles and 220–1000 nm for WPI-CS samples. As expected, a higher chitosan concentration conferred a 17% more positive zeta potential on chromium-entrapped WPI nanoparticles, whilst a higher dextran volume decreased the size of CS-DS nanoparticles by 32%. The addition of iron also caused a significant increase in size for all samples, as seen where the loaded WPI samples were 296 nm larger than the empty particles. Caco-2 iron absorption revealed that one formulation, which had the lowest particle size (226 ± 10 nm), caused a 64% greater iron absorption compared to the ferrous sulfate standard. This study describes, for the first time, the novel design of chromium- and iron-entrapped nanoparticles, which could act as novel systems for oral drug delivery

Takayasu arteritis in childhood: retrospective experience from a tertiary referral centre in the United Kingdom.

Takayasu arteritis (TA) is an idiopathic large-vessel vasculitis affecting the aorta and its major branches. Although the disease rarely affects children, it does occur, even in infants. The objective of this study was to evaluate the clinical features, disease activity, treatment and outcome of childhood TA in a tertiary UK centre

Steady State and Dynamic Modeling of Spiral Wound Wastewater Reverse Osmosis Process

yesReverse osmosis (RO)is one of the most important technologies used in wastewater treatment plants due to high contaminant rejection and low utilization of energy in comparison to other treatment procedures. For single-component spiral-wound reverse osmosis membrane process, one dimensional steady state and dynamic mathematical models have been developed based on the solution-diffusion model coupled with the concentration polarization mechanism. The model has been validated against reported data for wastewater treatment from literature at steady state conditions. Detailed simulation using the dynamic model has been carried out in order to gain deeper insight of the process. The effect of feed flow rate, pressure, temperature and concentration of pollutants on the performance of the process measured in terms of salt rejection, recovery ratio and permeate flux has been investigated.The full text will be available at the end of the publisher's embarg

Modeling of a spiral-wound reverse osmosis process and parameter estimation

YesReverse osmosis system has been widely used for the separation of organic and non-organic pollutants present in wastewater. The main aim of this study is to develop a one dimensional steady state model based on the three-parameter Spiegler-Kedem methodology using the gPROMS software and validate it by assessing the performance of membrane rejection for the separation data of aqueous solutions of phenol under different concentrations and pressures. Considerations of the variance of pressure, flow rate, solute concentration, solvent and solute fluxes and mass transfer coefficient along the feed channel were included in the model. Furthermore, an optimization methodology for the gEST parameter estimation tool has been developed in the gPROMS and used with experimental data in order to estimate the best values of the separation membrane parameters and the friction parameter. The simulation results of this model have been corroborated by experimental data

Wastewater Treatment by Spiral Wound Reverse Osmosis: Development and Validation of a Two Dimensional Process Model

yesReverse osmosis (RO) has become a significant method for removing salts and organic compounds from seawater and wastewater in recent decades. Spiral-wound module has been widely used due to a number of special features such as high packing density, premium separation and low operating cost. In this paper, a two-dimensional mathematical model is developed for the transport of dilute aqueous solutions through a spiral-wound RO module and the operational characteristics of the process under steady state conditions are analysed. The model is based on the solution-diffusion model coupled with the concentration polarization mechanism. This model yields a set of Differential and Algebraic Equations (DAEs), which are solved using the gPROMS software. The model is validated using experimental data from the literature for the rejection of dimethylphenol as solute in aqueous solutions. The model is then used to simulate the process under steady state conditions to gain deeper insight of the process

Development and Validation of N-nitrosamine Rejection Mathematical Model Using a Spiral-wound Reverse Osmosis Process

yesIn this paper, a one-dimensional mathematical model based on coupled differential and algebraic equations has been developed for analysing the separation mechanism of a N-nitrosamine in a spiral-wound reverse osmosis process. The model is based on Spiegler and Kedem’s work on mass transport and Darcy’s law and concentration polarization to analyse the pressure drop and mass transfer coefficient in the module feed channel respectively. The model is built using the gPROMS software suite and validated using N-nitrosamine rejection experimental data from the literature, obtained by using a pilot-scale cross-flow reverse osmosis filtration system. Analysis results derived from the model corroborate experimental data

Optimal reverse osmosis network configuration for the rejection of dimethylphenol from wastewater

YesReverse osmosis (RO) has long been recognised as an efficient separation method for treating and removing harmful pollutants, such as dimethylphenol in wastewater treatment. This research aims to study the effects of RO network configuration of three modules of a wastewater treatment system using a spiral-wound RO membrane for the removal of dimethylphenol from its aqueous solution at different feed concentrations. The methodologies used for this research are based on simulation and optimisation studies carried out using a new simplified model. This takes into account the solution-diffusion model and film theory to express the transport phenomena of both solvent and solute through the membrane and estimate the concentration polarization impact respectively. This model is validated by direct comparison with experimental data derived from the literature and which includes dimethylphenol rejection method performed on a small-scale commercial single spiral-wound RO membrane system at different operating conditions. The new model is finally implemented to identify the optimal module configuration and operating conditions that achieve higher rejection after testing the impact of RO configuration. The optimisation model has been formulated to maximize the rejection parameters under optimal operating conditions of inlet feed flow rate, pressure and temperature for a given set of inlet feed concentration. Also, the optimisation model has been subjected to a number of upper and lower limits of decision variables, which include the inlet pressure, flow rate and temperature. In addition, the model takes into account the pressure loss constraint along the membrane length commensurate with the manufacturer’s specifications. The research clearly shows that the parallel configuration yields optimal dimethylphenol rejection with lower pressure loss

Synthesis of novel acylated and esterified ciprofloxacin derivatives as efficient anticancer and antimicrobial agents

Nowadays, various factors enhance the resistance of some microbes to antibiotics. Irrational antibiotic use is considered an example of such factors. Therefore, the synthesis and reporting of heterocyclic compounds with multiple biological properties are of considerable value. Ciprofloxacin is an antibiotic used to treat infections. New amidification and esterification derivatives of ciprofloxacin were synthesized. Their structure was identified and confirmed using both proton and carbon-13 nuclear magnetic resonance, mass spectrometry, and elemental analysis. With the employment of MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-terazoliumbromide) methods, in vitro anticancer activity was evaluated. The utilization of clinical and laboratory standards institute (CLSI) instructions was involved in the in vitro antimicrobial activity evaluation of the newly synthesized derivatives. In terms of anticancer activity, cell proliferation, viability, and IC50, as well as antimicrobial activities, IZD (Inhibition Zone Diameter), MIC (Minimum Inhibitory Concentrations), MBC (Minimum Bactericidal Concentrations), and MFC (Minimum Fungicidal Concentration) were measured and reported. The lowest cell proliferation and viability and IC50 for 2,3-dihydroxypropyl 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylate (compound 5) were observed to be 27.12% and 7.83 μg/mL. In antimicrobial activity, the lowest MIC for 2,3-dihydroxypropyl 7-(4-benzoylpiperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylate (compound 6c) was observed to be 2 μg/mL (against Proteus mirabilis) and the lowest MIC for 1-cyclopropyl-6-fluoro-7-(4-(4-(methylthio)benzoyl)piperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (compound 3d) was observed to be 32 μg/mL (against Candida albicans, Aspergillus fumigatus). The effects were compared with commercially available drugs, and it was observed that some derivatives have the same efficacy as abemaciclib, which is used to treat breast cancer. Some derivatives were more effective than Cefazolin and Tolnaftate, well-known antibiotics and antifungals, respectively. Finally, a fairly clear relationship between the structure of the derivatives and their biological effectiveness was observed

Trends of Azole Antifungal Prescription in the United States: Medicare Part D Provider Utilization and Payment Data Analysis

BACKGROUND: Invasive fungal infections carry a substantial risk of mortality and morbidity. Azole antifungals are used in the treatment of such infections; however, their extensive use can lead to the emergence of antifungal resistance and increased costs to patients and healthcare systems. The aim of this study is to evaluate trends in these antifungals use and costs. METHODS: The secular and regional trends of outpatient azole antifungals were analyzed using Medicare Part D Prescriber Public Use Files for the years 2013-2020. The total days supply (TDS), total drug cost (TDC) per 100 000 enrollees, and cost per day (CPD) were evaluated. RESULTS: The azole antifungal TDS for Medicare Part D enrollees increased by 12% between 2013 and 2020, and increases were noted for each azole. Southern US regions had the highest TDS, with Arizona having the highest TDS among US states in 2020. Cost analysis showed that TDC of all azoles has increased by 93% over the years, going up from $123 316 in 2013 to$238 336 per 100 000 enrollees in 2020. However, CPD showed an increase only for fluconazole and isavuconazole, with CPD of $1.62 per day and$188.30 per day, respectively. CONCLUSIONS: Combined azole antifungal prescriptions TDS increased among Medicare Part D enrollees. The trend in CPD was mixed, whereas overall costs consistently increased over the same period. Such findings provide an insight into the impact of azole antifungal prescriptions, and increasing use could foreshadow more antifungal resistance. Continued studies to evaluate different prescribers\u27 trends are warranted