Spray-dried Cefixime Encapsulated Poly(lactide-co-glycolide) Microparticles: Characterization and Evaluation of In Vitro Release Kinetics with Antibacterial Activity

Our study reports on the development of novel biodegradable microparticles prepared by a spray-drying technique using the poly(lactide-co-glycolide) (PLGA), a biodegradable polymer for the controlled delivery of cefixime. Cefixime is a water-soluble drug having short biological half-life of 3 h. The behavior of PLGA in controlling drug release responses of cefixime microparticles was investigated. The resultant microparticles were characterized by scanning electron microscopy, encapsulation efficiency, particle-size distribution, X-ray diffraction, and in vitro dissolution studies (pH 7.2). To investigate the type of release mechanism that occurs, dissolution data were plotted according to different kinetic models. The in vitro release profiles from microparticles followed first order and Higuchi model release. Antibacterial studies were carried out using a standard agar diffusion method to determine the effectiveness of formulations in inhibiting the growth of microorganisms. It showed that the released drug from the formulations was effectively inhibiting the growth of microorganisms with the minimum inhibitory concentration of < 1 µg/mL. Data revealed the potential of formulations for treatment of infections caused by various microorganisms. Thus, this study demonstrates the high potential of the spray-drying technique to obtain stable cefixime microparticles with good encapsulation efficiency to achieve a delivery profile that would yield the controlled released level of the drug over a long period of time (74 h).     

SP3-FAIMS Chemoproteomics for High-Coverage Profiling of the Human Cysteinome**

Chemoproteomics has enabled the rapid and proteome-wide discovery of functional, redox-sensitive, and ligandable cysteine residues. Despite widespread adoption and considerable advances in both sample-preparation workflows and MS instrumentation, chemoproteomics experiments still typically only identify a small fraction of all cysteines encoded by the human genome. Here, we develop an optimized sample-preparation workflow that combines enhanced peptide labeling with single-pot, solid-phase-enhanced sample-preparation (SP3) to improve the recovery of biotinylated peptides, even from small sample sizes. By combining this improved workflow with on-line high-field asymmetric waveform ion mobility spectrometry (FAIMS) separation of labeled peptides, we achieve unprecedented coverage of >14000 unique cysteines in a single-shot 70 min experiment. Showcasing the wide utility of the SP3-FAIMS chemoproteomic method, we find that it is also compatible with competitive small-molecule screening by isotopic tandem orthogonal proteolysis–activity-based protein profiling (isoTOP-ABPP). In aggregate, our analysis of 18 samples from seven cell lines identified 34225 unique cysteines using only ∼28 h of instrument time. The comprehensive spectral library and improved coverage provided by the SP3-FAIMS chemoproteomics method will provide the technical foundation for future studies aimed at deciphering the functions and druggability of the human cysteineome.     

A Single Dose of Psilocybin Increases Synaptic Density and Decreases 5-HT2A Receptor Density in the Pig Brain

A single dose of psilocybin, a psychedelic and serotonin 2A receptor (5-HT_2AR) agonist, may be associated with antidepressant effects. The mechanism behind its antidepressive action is unknown but could be linked to increased synaptogenesis and down-regulation of cerebral 5-HT_2AR. Here, we investigate if a single psychedelic dose of psilocybin changes synaptic vesicle protein 2A (SV2A) and 5-HT_2AR density in the pig brain. Twenty-four awake pigs received either 0.08 mg/kg psilocybin or saline intravenously. Twelve pigs (n = 6/intervention) were euthanized one day post-injection, while the remaining twelve pigs were euthanized seven days post-injection (n = 6/intervention). We performed autoradiography on hippocampus and prefrontal cortex (PFC) sections with [³H]UCB-J (SV2A), [³H]MDL100907 (5-HT_2AR antagonist) and [³H]Cimbi-36 (5-HT_2AR agonist). One day post psilocybin injection, we observed 4.42% higher hippocampal SV2A density and lowered hippocampal and PFC 5-HT_2AR density (−15.21% to −50.19%). These differences were statistically significant in the hippocampus for all radioligands and in the PFC for [³H]Cimbi-36 only. Seven days post-intervention, there was still significantly higher SV2A density in the hippocampus (+9.24%) and the PFC (+6.10%), whereas there were no longer any differences in 5-HT_2AR density. Our findings suggest that psilocybin causes increased persistent synaptogenesis and an acute decrease in 5-HT_2AR density, which may play a role in psilocybin’s antidepressive effects.     

Development and Integration of a Data Acquisition System for SST-1 Phase-1 Plasma Diagnostics

Long pulse(of the order of 1000 s or more) SST-1 tokamak experiments demand a data acquisition system that is capable of acquiring data from various diagnostics channels without losing useful data(and hence physics information) while avoiding unnecessary generation of a large volume data.SST-1 Phase-1 tokamak operation has been envisaged with data acquisition of several essential diagnostics channels.These channels demand data acquisition at a sampling rate ranging from 1 kilo samples per second(KSPS) to 1 mega samples per second(MSPS).Considering the technical characteristics and requirements of the diagnostics,a data acquisition system based on PXI and CAMAC has been developed for SST-1 plasma diagnostics.Both these data acquisition systems are scalable.Present data acquisition needs involving slow plasma diagnostics are catered by the PXI based data acquisition system.On the other hand,CAMAC data acquisition hardware meets all requirements of the SST-1 Phase-1 fast plasma diagnostics channels.A graphical user interface for both data acquisition systems(PXI and CAMAC) has been developed using LabVIEW application development software.The collected data on the local hard disk are directly streaming to the central server through a dedicated network for post-shot data analysis.This paper describes the development and integration of the data acquisition system for SST-1 Phase-1 plasma diagnostics.The integrated testing of the developed data acquisition system has been performed using SST-1 central control and diagnostics signal conditioning units.In the absence of plasma shots,the integrated testing of the data acquisition system for the initial diagnostics of SST-1 Phase-1 operation has been performed with simulated physical signals.The primary engineering objective of this integrated testing is to validate the performance of the developed data acquisition system under simulated conditions close to that of actual tokamak operation.The data acquisition is synchronized with a clock and trigger provided by the central timing system.     

Grafting of low density poly(ethylene) with butyl acrylate: Synthesis and characterisation

Low density poly(ethylene) was grafted with butyl acrylate using benzoyl peroxide as free radical initiator in an inert atmosphere and toluene as solvent. Various parameters such as reaction time, temperature, initiator concentration and ratio of monomer to polymer were varied to study their effects on percentage of grafting and grafting efficiency of butyl acrylate on to low density poly(ethylene). The graft copolymers were characterised by IR spectroscopy. The change in the solubility behaviour of low density poly(ethylene) due to grafting was studied by turbidometric titration. Thermal stability of graft copolymers was found to be higher than that of LDPE. Intrinsic viscosity data showed an increase in viscosity with increasing grafting percentage.     

Learning multicriteria fuzzy classification method PROAFTN from data

In this paper, we present a new methodology for learning parameters of multiple criteria classification method PROAFTN from data. There are numerous representations and techniques available for data mining, for example decision trees, rule bases, artificial neural networks, density estimation, regression and clustering. The PROAFTN method constitutes another approach for data mining. It belongs to the class of supervised learning algorithms and assigns membership degree of the alternatives to the classes. The PROAFTN method requires the elicitation of its parameters for the purpose of classification. Therefore, we need an automatic method that helps us to establish these parameters from the given data with minimum classification errors. Here, we propose variable neighborhood search metaheuristic for getting these parameters. The performances of the newly proposed method were evaluated using 10 cross validation technique. The results are compared with those obtained by other classification methods previously reported on the same data. It appears that the solutions of substantially better quality are obtained with proposed method than with these former ones.     

Polymeric prodrug: Synthesis,release study and antimicrobial property of poly(styrene-co-maleic anhydride)-bound acriflavine

The release behaviour of poly(methyl methacrylate-co-maleic anhydride)-bound acriflavine was compared with that of acriflavine bound to poly(styrene-co-maleic anhydride), the latter copolymer was prepared by solution polymerization and characterised. Acriflavine was covalently bound on the surface of the copolymer matrix in N,N-dimethylformamide using triethylamine as catalyst. The amount of acriflavine covalently bound to poly(styrene-co-maleic anhydride) was studied as a function of time and concentration. The in vitro drug release kinetics of acriflavine in weakly basic medium and the antimicrobial activity of the released drug were established.     

Rheological Properties of Leucaena glauca Gum in Aqueous Solutions

The flow properties of Leucaena glauca gum solutions were studied in the range of shear rates 1.5 to 1310 s⁻¹, using a rotational viscometer Rheotest 2. The flow behaviour of aqueous solutions of the polysaccharide is pseudoplastic, and transition from Newtonian to pseudoplastic behaviour occurs in the low shear rate range at concentrations of interest to the industry. The flow of polysaccharide solutions is described by equation of state proposed by M. M. Cross. The basic rheological parameters, like zero shear rate viscosity (η_o), infinite shear rate viscosity (ηα) and a constant associated with the rupture of linkages (α) were calculated applying simple and established relations. The effect of concentration and temperature on rheological parameters have been studied. The Cross equation is found to be applicable to the data with a good degree of accuracy over a wide range of shear rates.     

Catalysis and stability of an alkaline protease from a haloalkaliphilic bacterium under non-aqueous conditions as a function of pH, salt and temperature

A haloalkaliphilic bacterium, isolated from Coastal Gujarat (India) was identified as Oceanobacillus sp. (GQ162111) based on 16S rRNA gene sequence. The organism grew and secreted extra cellular protease in presence of various organic solvents. At 30% (v/v) concentration of hexane, heptane, isooctane, dodecane and decane, significant growth and protease production was evident. The alkaline protease was purified in a single step on phenyl sepharose 6 FF with 28% yield. The molecular mass as judged by SDS-PAGE was 30?kDa. The temperature optimum of protease was 50°C and the enzyme retained 70% activity in 10% (v/v) isooctane. Effect of salt and pH was investigated in combination to assess the effect of isooctane. In organic solvents, the enzyme was considerably active at pH 8-11, with optimum activity at pH 10. Salt at 2?M was optimum for activity and enzyme maintained significant stability up to 18?h even at 3?M salt concentration. Patters of growth, protease production, catalysis and stability of the enzyme are presented. The study resumes significance as limited information is available on the interaction of haloalkaliphilic bacteria and their enzymes with organic solvents.