Chitosan-dextran sulphate nanocapsule drug delivery system as an effective therapeutic against intraphagosomal pathogen Salmonella

Objectives: The ability to target conventional drugs efficiently inside cells to kill intraphagosomal bacteria has been a major hurdle in treatment of infective diseases. We aimed to develop an efficient drug delivery system for combating infection caused by Salmonella, a well-known intracellular and intraphagosomal pathogen. Chitosan dextran sulphate (CD) nanocapsules were assessed for their efficiency in delivering drugs against Salmonella. Methods: The CD nanocapsules were prepared using the layer-by-layer method and loaded with ciprofloxacin or ceftriaxone. Antibiotic-loaded nanocapsules were analysed in vitro for their ability to enter epithelial and macrophage cells to kill Salmonella. In vivo pharmacokinetics and organ distribution studies were performed to check the efficiency of the delivery system. The in vivo antibacterial activity of free antibiotic and antibiotic loaded into nanocapsules was tested in a murine salmonellosis model. Results: In vitro and in vivo experiments showed that this delivery system can be used effectively to clear Salmonella infection, CD nanocapsules were successfully employed for efficient targeting and killing of the intracellular pathogen at a dosage significantly lower than that of the free antibiotic. The increased retention time of ciprofloxacin in the blood and organs when it was delivered by CD nanocapsules compared with the conventional routes of administration may be the reason underlying the requirement for a reduced dosage and frequency of antibiotic administration. Conclusions: CD nanocapsules can be used as an efficient drug delivery system to treat intraphagosomal pathogens, especially Salmonella infection, This delivery system might be used effectively for other vacuolar pathogens including Mycobacteria, Brucella and Legionella.

System reliability analysis of granular filter for protection against piping in dams

Granular filters are provided for the safety of water retaining structure for protection against piping failure. The phenomenon of piping triggers when the base soil to be protected starts migrating in the direction of seepage flow under the influence of seepage force. To protect base soil from migration, the voids in the filter media should be small enough but it should not also be too small to block smooth passage of seeping water. Fulfilling these two contradictory design requirements at the same time is a major concern for the successful performance of granular filter media. Since Terzaghi era, conventionally, particle size distribution (PSD) of granular filters is designed based on particle size distribution characteristics of the base soil to be protected. The design approach provides a range of D15f value in which the PSD of granular filter media should fall and there exist infinite possibilities. Further, safety against the two critical design requirements cannot be ensured. Although used successfully for many decades, the existing filter design guidelines are purely empirical in nature accompanied with experience and good engineering judgment. In the present study, analytical solutions for obtaining the factor of safety with respect to base soil particle migration and soil permeability consideration as proposed by the authors are first discussed. The solution takes into consideration the basic geotechnical properties of base soil and filter media as well as existing hydraulic conditions and provides a comprehensive solution to the granular filter design with ability to assess the stability in terms of factor of safety. Considering the fact that geotechnical properties are variable in nature, probabilistic analysis is further suggested to evaluate the system reliability of the filter media that may help in risk assessment and risk management for decision making.

Spectral intensity distribution of trapped

To calculate static response properties of a many-body system, local density approximation (LDA) can be safely applied. But, to obtain dynamical response functions, the applicability of LDA is limited bacause dynamics of the system needs to be considered as well. To examine this in the context of cold atoms, we consider a system of non-interacting spin4 fermions confined by a harmonic trapping potential. We have calculated a very important response function, the spectral intensity distribution function (SIDF), both exactly and using LDA at zero temperature and compared with each other for different dimensions, trap frequencies and momenta. The behaviour of the SIDF at a particular momentum can be explained by noting the behaviour of the density of states (DoS) of the free system (without trap) in that particular dimension. The agreement between exact and LDA SIDFs becomes better with increase in dimensions and number of particles.

Anomalous lifetime statistics of ligand-receptor binding in a tethered polymer system

In this paper, motivated by observations of non-exponential decay times in the stochastic binding and release of ligand-receptor systems, exemplified by the work of Rogers et al on optically trapped DNA-coated colloids (Rogers et al 2013 Soft Matter 9 6412), we explore the general problem of polymer-mediated surface adhesion using a simplified model of the phenomenon in which a single polymer molecule, fixed at one end, binds through a ligand at its opposite end to a flat surface a fixed distance L away and uniformly covered with receptor sites. Working within the Wilemski-Fixman approximation to diffusion-controlled reactions, we show that for a flexible Gaussian chain, the predicted distribution of times f(t) for which the ligand and receptor are bound is given, for times much shorter than the longest relaxation time of the polymer, by a power law of the form t(-1/4). We also show when the effects of chain stiffness are incorporated into this model (approximately), the structure of f(t) is altered to t(-1/2). These results broadly mirror the experimental trends in the work cited above.

Fully 3D refraction correction dosimetry system

The irradiation of selective regions in a polymer gel dosimeter results in an increase in optical density and refractive index (RI) at those regions. An optical tomography-based dosimeter depends on rayline path through the dosimeter to estimate and reconstruct the dose distribution. The refraction of light passing through a dose region results in artefacts in the reconstructed images. These refraction errors are dependant on the scanning geometry and collection optics. We developed a fully 3D image reconstruction algorithm, algebraic reconstruction technique-refraction correction (ART-rc) that corrects for the refractive index mismatches present in a gel dosimeter scanner not only at the boundary, but also for any rayline refraction due to multiple dose regions inside the dosimeter. In this study, simulation and experimental studies have been carried out to reconstruct a 3D dose volume using 2D CCD measurements taken for various views. The study also focuses on the effectiveness of using different refractive-index matching media surrounding the gel dosimeter. Since the optical density is assumed to be low for a dosimeter, the filtered backprojection is routinely used for reconstruction. We carry out the reconstructions using conventional algebraic reconstruction (ART) and refractive index corrected ART (ART-rc) algorithms. The reconstructions based on FDK algorithm for cone-beam tomography has also been carried out for comparison. Line scanners and point detectors, are used to obtain reconstructions plane by plane. The rays passing through dose region with a RI mismatch does not reach the detector in the same plane depending on the angle of incidence and RI. In the fully 3D scanning setup using 2D array detectors, light rays that undergo refraction are still collected and hence can still be accounted for in the reconstruction algorithm. It is found that, for the central region of the dosimeter, the usable radius using ART-rc algorithm with water as RI matched medium is 71.8%, an increase of 6.4% compared to that achieved using conventional ART algorithm. Smaller diameter dosimeters are scanned with dry air scanning by using a wide-angle lens that collects refracted light. The images reconstructed using cone beam geometry is seen to deteriorate in some planes as those regions are not scanned. Refraction correction is important and needs to be taken in to consideration to achieve quantitatively accurate dose reconstructions. Refraction modeling is crucial in array based scanners as it is not possible to identify refracted rays in the sinogram space.