Influence of solvent mixtures on HPMCAS-celecoxib microparticles prepared by electrospraying

Hypromellose acetate succinate(HPMCAS) microparticles containing the poorly-water soluble drug celecoxib(CEL) were prepared by electrospraying intended for oral drug delivery. Various solvent mixtures with different solubility for CEL and HPMCAS were used to induce changes in the polymer structural conformation of the microparticles. The performance of the prepared microparticles was evaluated by studying the solid state from, particle size and morphology, radial drug distribution and drug release. CEL was amorphous in all electrosprayed HPMCAS microparticles. The particle size and morphology was dependent on the solubility of HPMCAS in the solvent mixture used with poorer solvents resulting in smaller microparticles with rougher appearance. The CEL distribution on the particles surface was relatively homogeneous and similar for all microparticles. Drug release from the microparticles was observed at a higher rate depending on the solubility of HPMCAS in the solvent used for electrospraying, and in all cases an at least 4-fold higher rate was observed compared with the crystalline drug. Drug precipitation from the supersaturated solution was inhibited by HPMCAS for all microparticles based on its parachute effect while crystalline CEL did not reach supersaturation. This study demonstrated that electrospraying can be used to produce microparticles with tailored properties for pharmaceutical application by adjusting solvent selection.

Polymer-based nanoparticulate solid dispersions prepared by a modified electrospraying process

A modified electrospraying process is exploited to enhance the dissolution profiles of a poorly water-soluble drug. With polyvinylpyrrolidone (PVP) as a hydrophilic polymer matrix and ketoprofen (KET) as a model drug, polymer-drug composites in the form of nanoparticles were prepared and characterized. The surface morphologies, the physical status of the drug, and the drug-polymer interactions were studied using FESEM, DSC, XRD, and ATR-FTIR. FESEM observations demonstrated that the nanoparticles gradually decreased in size from 640 ± 350, to 530 ± 320, 460 ± 200 and 320 ± 160 nm as the KET content increased from 0, to 9.1%, 16.7% and 33.3% w/w, respectively. Results from DSC and XRD suggested that KET was distributed in the PVP matrix in an amorphous manner at the molecular level. This is thought to be due to their compatibility, arising through hydrogen bonding as demonstrated by ATR- FTIR spectra. In vitro dissolution tests showed that the nanoparticles released the incorporated KET within 1 min, evidencing markedly improved dissolution over pure KET and a KET-PVP physical mixture. Electrospraying can hence offer a facile route to develop new polymer composites for biomedical applications, in particular for improving dissolution rate of poorly water-soluble drugs.

ELECTROSPRAYING/ELECTROSPINNING OF POLY(γ-STEARYL-LGLUTAMATE):FORMATION OF SURFACES WITH SUPERHYDROPHOBICITY

Electrospraying/electrospinning of poly(γ-stearyl-L-glutamate) (PSLG) was investigated on a series solutions with different concentrations in chloroform.Field emission scanning electron microscopy (FESEM) and attenuated Iotal reflectance Fourier transform infrared spectroscopy (FT-IR/ATR) were used to characterize the morphology and structure of the electrosprayed/electrospun polypeptide mats.It was found that electrospraying of PSLG with concentrations lower than 16 wt% afforded beads,while microfibers cou...

Preparation of TiO2 and SiC Films from Their Precursors Using Electrospraying

Titanium dioxide(TiO2) films were prepared by cone - jet mode electrospraying a titanium ethoxideprecursor solution onto a silicon substrate.The effects of spraying time,substrate temperature and aging on thesurface morphology of the films prepared were studied.Thin films obtained after spraying for 600 s were aged atroom temperature to form a porous TiO2 network with pores in the size range of 100 - 500 nm.Thicker filmswere prepared by spraying for 3 000 s,but these cracked on drying although it can be concluded that films pre-pared using a higher substrate temperature were denser.By this method,SiC coating was also prepared on anAl2O3 substrate using polysilane as a precursor.The result implies the potential of an industrial production ofdye sensitized solar cells by electrospraying technique.

Wastewater Decontamination from Microorganisms by Electrospraying Corona Discharge

A novel water treatment technique, based on a combination of electrospraying and pulsed corona discharge, has been used for bio-decontamination of wastewater. The electrospraying process has been found to increase the surface area of the treated wastewater, and hence increases the efficiency of the corona treatment process. The phase diagram of the discharge, which characterizes the discharge regimes, has been identified experimentally. The survival ratio of the microorganisms has been investigated experimentally as a function of the applied voltage and the numbers of treatment runs using air and oxygen as working gases. Microorganism surface has been examined using scanning electron microscope (SEM), which enabled in understanding the decontamination mechanisms of the treated microorganism. A complete decontamination has been achieved after only one run for an applied voltage higher than 16 kV when the discharge system was operated in oxygen gas. Optical emission spectrum of the electrosprayed water confirmed the existence of OH-radicals responsible for decontamination process.

Generation of biomaterial particles with controlled dimensions via electrospraying

It is well known that small biomaterial particles can lead to superior properties demanded by advanced applications in tissue engineering. Electrospraying has been considered as a promising approach to prepare fine particles, but reducing the particle size during such jetting process is always challenging. This is because the size of the as-sprayed particles is always limited by the device outlet diameter used. In the study we show that hydroxyapatite (HA) relics of 2 - 3 μm with low standard deviation can be deposited using a large nozzle (diameter of 1100 μm) only by reducing the nozzle tip angle from 90° to 15°. The mechanism of such phenomenon was extensively discussed, and a range of refined HA patterns were successfully prepared using the updated electrspraying configuration. We anticipate our findings to have a significant impact on the research of nanostructured biomaterials with superior properties which are realized by reducing the particle size using a greener electrically-driven processing technique.

Fabrication and photocatalytic activity of TiO2 composite membranes via simultaneous electrospinning and electrospraying process

In present study, a simultaneous electrospinning and electrospraying（SEE） process was employed to produce microclusters of TiO2 nanoparticles and interlock them in nanofibrous network. The photocatalytic composite membranes（PCMs） were fabricated by electrospraying TiO2 nanoparticle suspension into microcluster form that dispersed and entrapped within nylon-6 electrospun fiber membrane. Three PCMs membrane with TiO2 content of 52.0, 83.6,and 91.7 wt.% were successfully fabricated. The membrane consisted of TiO2 microclusters,ranging in sizes from around 0.3 to 10 μm, distributed uniformly within the nylon-6 nanofibrous network. PCMs photocatalytic activity against Methylene Blue（MB） in aqueous solution showed more than 98% MB removal efficiency after 120 min of photocatalytic oxidation（PCO） for all PCMs. For PCM with the highest TiO2 content tested for 5 PCO cycles, it was found that most of their TiO2 content remained incorporated within the nanofibrous structure. The concept of nanoparticles clusters entrapment with SEE fabrication employed here provide a simple and effective method for reducing detachment of nanostructure phase from nanocomposite membrane.

Epoxy microcapsules for high-performance self-healing materials using a novel method via integrating electrospraying and interfacial polymerization

The high-efficiency fabrication of high-quality microcapsules containing epoxy is crucial to the further development of the potential practical self-healing epoxy systems based on microencapsulated two-part epoxy-amine chemistry.Herein,a novel microencapsulation technique based on non-equilibrium droplets via integrating electrospraying and interfacial polymerization(ES-IP)was established to efficiently microencapsulate epoxy monomers.The ES-IP technique,consisting of three continuous steps,i.e.electrospraying to massively generate droplets,enwrapping every single droplet through instant interfacial polymerization,and thickening shell at an elevated temperature,has great flexibility to regulate the microencapsulation process and the microcapsule quality.The fabricated core-shell structured epoxy microcapsules(Ep-MCs)were comprehensively characterized for their properties,showing that they have high cleanness with rare impurities,controllable and tunable size,good thermal stability and tightness,and high effective core fraction.The high-quality Ep-MCs were adopted to formulate a self-healing epoxy based on the microencapsulated epoxy-amine chemistry.The highest healing efficiency,in terms of the recovered mode I fracture toughness,of 110±17%was achieved after being healed at room temperature(~25℃)for 48 h.While the developed ES-IP technique facilitates the microencapsulation technique based on non-equilibrium droplets,the fabricated high-quality Ep-MCs greatly promote the further developments of the practical self-healing materials.

Red-blood-cell-shaped chitosan microparticles prepared by electrospraying

Red-blood-cell-shaped chitosan microparticles with acid-triggered dissolution and auto-fluorescence were successfully fabricated by a simple strategy combining electrospraying with a solvent diffusion process controlled by solvent evaporation. The sizes of the prepared chitosan microparticles were rela- tively uniform. Control of the solvent diffusion process was crucial for the formation of microparticles with concave morphology. A chitosan aqueous solution containing 20vo1% ethanol as the evaporable solvent and 30 vol% dimethyl sulfoxide as the diffusible solvent was optimal for preparation of chitosan microparticles with the desired red-blood-cell-like size and shape. These chitosan microparticles will be highly attractive for many biological and biomedical aoolications.

Experimental study of the effect of gas discharge on ionic liquid electrospray

Ionic liquid electrospray(ILE) in an atmospheric environment is often accompanied by the gas discharge phenomenon. It interferes with the normal operation of the electrospray and the measurement of experimental parameters. In this study, electrospray experiments were conducted on the ionic liquid EMI-BF4. The observations revealed that the operating modes of the ionic liquid depend on the voltage polarity at high voltages. Additionally, a correspondence between the operating mode of ILE and the current signal in the circuit was established. The shape of the liquid cone formed at the needle tip bore a striking resemblance to the plume of corona discharge, suggesting that the motion trajectory of electrons influenced the curvature of the liquid cone. Steamer theory provided a clear explanation for the change in curvature as the voltage increased.

Structure Controlling and Adsorption Application of Polyethersulfone Porous Microspheres Prepared via Electrospraying

The focus of this work is to control the structure of electrosprayed polymer microspheres and then study the effect of different structures on the microspheres＇ adsorption properties. Scanning electron microscopy （SEM） coupled with image analysis software was employed to evaluate the size distributions and the structure of microspheres. According to the observation and analysis results, two types of polyethersulfone （PES） porous microspheres （perfect sphere-shaped and collapsed） were prepared via electrospraying technology by adjusting the solvent and polymer molecular weight. The porous PES microspheres can remove bisphenol A （BPA） from its aqueous solution effectively. Compared with collapsed microspheres, the rough microspheres had much higher specific surface area and better mobility in the BPA aqueous solution, so it showed a better adsorption capacity than that of collapsed microspheres. The solvent evaporation rate and the occurrence rate of phase separation significantly affect the structure and morphology of microspheres.

Hierarchically electrospraying a PLGA@chitosan sphere-in-sphere composite microsphere for multi-drug-controlled release

Sequential administration and controlled release of different drugs are of vital importance for regulating cellular behaviors and tissue regeneration,which usually demands appropriate carriers like microspheres(MS)to control drugs releases.Electrospray has been proven an effective technique to prepare MS with uniform particle size and high drug-loading rate.In this study,we applied electrospray to simply and hierarchically fabricate sphere-in-sphere composite microspheres,with smaller poly(lactic-co-glycolic acid)MS(~8-10 lm in diameter)embedded in a larger chitosan MS(~250-300 lm in diameter).The scanning electron microscopy images revealed highly uniform MS that can be accurately controlled by adjusting the nozzle diameter or voltage.Two kinds of model drugs,bovine serum albumin and chlorhexidine acetate,were encapsulated in the microspheres.The fluorescence-labeled rhodamine-fluoresceine isothiocyanate(Rho-FITC)and ultraviolet(UV)spectrophotometry results suggested that loaded drugs got excellent distribution in microspheres,as well as sustained,slow release in vitro.In addition,far-UV circular dichroism and matrixassisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS)results indicated original secondary structure and molecular weight of drugs after electrospraying.Generally speaking,our research proposed a modified hierarchically electrospraying technique to prepare sphere-in-sphere composite MS with two different drugs loaded,which could be applied in sequential,multi-modality therapy.

Preparation of multicore millimeter-sized spherical alginate capsules to specifically and sustainedly release fish oil

Specific and sustained release of nutrients from capsules to the gastrointestinal tract has attracted many attentions in the field of food and drug delivery.In this work,we reported a monoaxial dispersion electrospraying-ionotropic gelation technique to prepare multicore millimeter-sized spherical capsules for specific and sustained release of fish oil.The spherical capsules had diameters from 2.05 mm to 0.35 mm with the increased applied voltages.The capsules consisted of uniform(at applied voltages of≤10 k V)or nonuniform(at applied voltages of>10 k V)multicores.The obtained capsules had reasonable loading ratios(9.7%-6.3%)due to the multicore structure.In addition,the obtained capsules had specific and sustained release behaviors of fish oil into the small intestinal phase of in vitro gastrointestinal tract and small intestinal tract models.The simple monoaxial dispersion electrospraying-ionotropic gelatin technique does not involve complicated preparation formulations and polymer modification,which makes the technique has a potential application prospect for the fish oil preparations and the encapsulation of functional active substances in the field of food and drug industries.

Identification,structure elucidation and origin of a common pyridinium-thiocyanate intermediate in electrospray mass spectrometry among the benziamidazole-class proton pump inhibitors

During the analysis of benziamidazole-class irreversible proton pump inhibitors,an unusual mass spectral response with the mass-to-charge ratio at[Mt10]t intrigued us,as it couldn't be assigned to any literature known relevant structure,intermediate or adduct ion.Moreover,this mysterious mass pattern of[Mt10]t has been gradually observed by series of marketed proton pump inhibitors,viz.omeprazole,pantoprazole,lansoprazole and rabeprazole.All the previous attempts to isolate the corresponding component were unsuccessful.The investigation of present work addresses this kind of signal to a pyridinium thiocyanate mass spectral intermediate(10),which is the common fragment ion of series of labile aggregates.The origin of such aggregates can be traced to the reactive intermediates formed by acid-promoted degradation.These reactive intermediates tend to react with each other and give raise series of complicated aggregates systematically in a water/acetonitrile solution by electrospray ionization.The structure of the corresponding pyridinium thiocyanate species of omeprazole(10a)has been eventually characterized with the help of synthetic specimen(10a′).Our structural proposal as well as its origin was supported by in situ nuclear magnetic resonance,chemical derivatization and colorimetric experiments.

Comparison of different approaches for direct coupling of solid-phase microextraction to mass spectrometry for drugs of abuse analysis in plasma

The direct coupling of solid-phase microextraction(SPME)to mass spectrometry(MS)(SPME-MS)has proven to be an effective method for the fast screening and quantitative analysis of compounds in complex matrices such as blood and plasma.In recent years,our lab has developed three novel SPME-MS techniques:SPME-microfluidic open interface-MS(SPME-MOI-MS),coated blade spray-MS(CBS-MS),and SPME-probe electrospray ionization-MS(SPME-PESI-MS).The fast and high-throughput nature of these SPME-MS technologies makes them attractive options for point-of-care analysis and anti-doping testing.However,all these three techniques utilize different SPME geometries and were tested with different MS instruments.Lack of comparative data makes it difficult to determine which of these methodologies is the best option for any given application.This work fills this gap by making a comprehensive comparison of these three technologies with different SPME devices including SPME fibers,CBS blades,and SPME-PESI probes and SPME-liquid chromatography-MS(SPME-LC-MS)for the analysis of drugs of abuse using the same MS instrument.Furthermore,for the first time,we developed different desorption chambers for MOI-MS for coupling with SPME fibers,CBS blades,and SPME-PESI probes,thus illustrating the universality of this approach.In total,eight analytical methods were developed,with the experimental data showing that all the SPME-based methods provided good analytical performance with R^(2)of linearities larger than 0.9925,accuracies between 81%and 118%,and good precision with an RSD%≤13%.

Rapid authentication of different herbal medicines by heating online extraction electrospray ionization mass spectrometry

The rapid and accurate authentication of traditional Chinese medicines(TCMs)has always been a key scientific and technical problem in the field of pharmaceutical analysis.Herein,a novel heating online extraction electrospray ionization mass spectrometry(H-oEESI-MS)was developed for the rapid and direct analysis of extremely complex substances without the requirement for any sample pretreatment or pre-separation steps.The overall molecular profile and fragment structure features of various herbal medicines could be completely captured within 10–15 s,with minimal sample(<0.5 mg)and solvent consumption(<20μL for one sample).Furthermore,a rapid differentiation and authentication strategy for TCMs based on H-oEESI-MS was proposed,including metabolic profile characterization,characteristic marker screening and identification,and multivariate statistical analysis model validation.In an analysis of 52 batches of seven types of Aconitum medicinal materials,20 and 21 key compounds were screened out as the characteristic markers of raw and processed Aconitum herbal medicines,respectively,and the possible structures of all the characteristic markers were comprehensively identified based on Compound Discoverer databases.Finally,multivariate statistical analysis showed that all the different types of herbal medicines were well differentiated and identified(R^(2)X>0.87,R^(2)Y>0.91,and Q^(2)>0.72),which further verified the feasibility and reliability of this comprehensive strategy for the rapid authentication of different TCMs based on H-oEESI-MS.In summary,this rapid authentication strategy realized the ultra-high-throughput,low-cost,and standardized detection of various complex TCMs for the first time,thereby demonstrating wide applicability and value for the development of quality standards for TCMs.

固相萃取-超高效液相色谱-电喷雾串联质谱法同时测定地表水中16种全氟有机化合物

建立了固相萃取-超高效液相色谱-电喷雾串联三重四极杆质谱联用技术分析水中16种全氟有机化合物的高通量检测方法。样品经 WAX 固相萃取柱富集和净化后，采用 Waters ACQUITY UPLCTM BEH C18色谱柱，含2 mmol/L乙酸铵的甲醇和含2 mmol/L乙酸铵的水作为流动相进行梯度洗脱，质谱采用电喷雾负离子电离，多反应监测模式检测。16种全氟有机化合物在0.5~100μg/L或1.0~100μg/L 浓度范围内线性关系良好，相关系数为0.9987~0.9999，方法的检出限为0.06~0.46 ng/L；高、中、低3个添加水平的回收率为67.6％~103％，相对标准偏差为2.94％~12.0％。结果表明，该方法灵敏、准确且检测范围广，分析速度快，是一种适于实际水样中全氟有机化合物检测分析的方法。

电喷雾解吸电离质谱法直接测定蔬菜表面的莠去津残留

A direct determination method for the atrazine residue on the vegetable was developed by using desorption electrospray ionization mass spectrometry (DESI MS) without any sample pretreatment.Acetonitrile-water (1:1,v/v),which contained 0.1% formic acid,was used as the spray solvent.The working conditions,such as ESI gas inlet pressure,ESI flow rate,ESI spray voltage,spray-to-sample distance,spray-to-cone-hole distance and the collision induced dissociation (CID) voltage for MS/MS,were optimized for both DESI and esquires 6 000 mass spectrometer.The linear range of atrazine on cabbage leaves was 25.25-2 525 pg/mm2,the R2 was 0.991 6,and the relative standard deviations were between 3.37% and 26.17%.The LOD of atrazine calculated by S/N=3 was 2.50 pg/mm2.

β-环糊精与蛋白质非共价复合物的电喷雾质谱研究

电喷雾质谱(ESI-MS)已经广泛应用于非共价复合物的检测和研究[1,2].ESI是一种极软的离子化过程,它不仅能在不断裂共价键的情况下使分子离子化,而且可以在离子化过程中保持分子间弱的非共价键作用.……

液相色谱-电喷雾离子阱质谱法测定贝类中软骨藻酸

记忆缺失性贝类毒素(amnesic shellfish toxin,简称ASP)主要成分软骨藻酸(domoic acid,简称DA)是一种氨基酸类的生理活性物质(图1),因最早从红藻属的树枝软骨藻(chondria armata)分离出来而被命名为软骨藻酸.……