In vitro release dynamics of model drugs from psyllium and acrylic acid based hydrogels for the use in colon specific drug delivery

Psyllium is medicinally important gel forming polysaccharides. Keeping in view, the pharmacological importance of psyllium and drug delivery devices based on hydrogels, psyllium, if suitably tailored to prepare the hydrogels, can act as the double potential candidates for the novel drug delivery systems. Therefore, it is an attempt to prepared psyllium and acrylic acid based pH sensitive novel hydrogels by using N,N'-methylenebisacrylamide (N,N-MBAAm) as crosslinker and ammonium persulfate (APS) as initiator for the use in colon specific drug delivery. The present paper discusses the swelling kinetics of the hydrogels and release dynamics of model drugs (tetracycline hydrochloride, insulin and tyrosine) from drug-loaded hydrogels, for the evaluation of the swelling mechanism and drug release mechanism from the polymeric networks .The effect of pH on the swelling kinetics and release pattern of drugs have been studied by varying the pH of the release medium. It has been observed that swelling and release of drugs from the hydrogels occurred through non-Fickian or anomalous diffusion mechanism in distilled water and pH 7.4 buffer. It shows that the rate of polymer chain relaxation and the rate of drug diffusion from these hydrogels are comparable.     

Biogenic gold nanoparticles as fotillas to fire berberine hydrochloride using folic acid as molecular road map

Use of biologically modified gold nanoparticles (GNPs) as molecular vehicle to ferry potential anti-cancer drug berberine hydrochloride (BHC) using folic acid (FA) as targeting molecule is reported in this work. A tropical fruit peel, Trapa bispinosa is used to fabricate highly monodispersed GNPs, passivated with essential functional groups which were used as linkers to attach FA and BHC via amide linkage. Flocculation Parameter (FP) of biologically synthesized GNPs was calculated under different salt concentrations which were found to be very ideal under a physiological condition. Various statistical models were used to find drug release profile out of which Higuchi was found to be the most ideal. GNP–FA–BHC complexes were found to be active against folic acid expressing HeLa cells.     

Digraph and matrix method for the performance evaluation of carbide compacting die manufactured by wire EDM

This paper presents a methodology to evaluate the performance of carbide compacting die using graph theoretic approach (GTA). Factors affecting the die performance and their interactions are analysed by developing a mathematical model using digraph and matrix method. Permanent function or die performance index is obtained from the matrix model developed from the digraphs. This permanent function/index value compares and ranks the factors affecting the die performance. It helps in selection of optimum process parameters during die manufacturing. Hence, process output errors such as dimensional inaccuracy, large surface craters, deep recast layers, etc. will be minimised during die manufacturing which helps to achieve better die performance. In present illustration, factors affecting the performance of carbide compacting die are grouped into five main factors namely work material, machine tool, tool electrode, geometry of die and machining operation. GTA methodology reveals that the machine tool has highest index value. Therefore, it is the most influencing factor affecting the die performance. In case of die material low cobalt concentration and small grain size yields good surface finish, while in machine tool low discharge energy (i.e. low values of peak current, pulse-on time, servo voltage and high value of pulse-off time) and high dielectric flow rate yields good surface finish and, hence, favours the good die performance. In case of die geometry, large work piece thickness and small taper angles results in lesser geometrical deviations and hence helps to achieve better die performance.     

In-vitro drug release kinetics studies of mesoporous SBA-15-azathioprine composite

The mesoporous silica (or SBA-15) was loaded with azathioprine drug. Azathioprine drug was incorporated into mesoporous silica by post impregnation method to reduce its toxic effects by controlling the drug release property. The synthesized pure SBA-15 and SBA-15-azathioprine composite were characterized by UV–visible spectrophotometry, thermo-gravimetric analysis, small and large angle powder X-ray diffraction, field emission scanning electron microscopy, high resolution transmission electron microscopy, Fourier transform infrared spectroscopy and nitrogen adsorption–desorption analysis. The successful inclusion of azathioprine drug in host material SBA-15 was confirmed by the reduced surface area (114 m²/g) and pore diameter (6.5 nm) of the organic–inorganic composite material. The drug entrapment efficiency of 90.67 % and loading efficiency of 72.67 % was achieved. The azathioprine drug release process from the mesoporous silica to simulated gastric, intestinal and body fluid were examined and the controlled release effect of the azathioprine drug in all fluids were studied. The Korsmeyer–Peppas model fits well the drug release data with the non-Fickian diffusion model and zero order kinetics for produced mesoporous silica. The controlled drug release enhanced the bioavailability and reduces its repeated administration. Hence, the composite drug can reduce the toxicity and side effects of the azathioprine.     

CD73 and PD-L1 as Potential Therapeutic Targets in Gallbladder Cancer

Gallbladder cancer (GBC) is one of the most common and aggressive biliary tract cancers with a dismal prognosis. Ongoing clinical trials are evaluating a few selected immune checkpoint inhibitors (ICIs) as monotherapy for the treatment of GBC patients. However, only a subset of patients benefits from these treatments. To improve ICI therapy response, molecular mechanisms that confer resistance to immune checkpoint (IC) blockade needs to be explored. Epithelial-to-mesenchymal transition (EMT) program and cancer stem cells (CSCs) have been implicated as key processes that confer ICI treatment resistance. However, in GBC the EMT-CSC-IC axis has not yet been clearly elucidated. This study aims to examine the aberrant expression of ICs associated with CSC and EMT. We successfully enriched CSCs by utilizing a 3-dimensional culture system and established a reversible EMT model with human GBC NOZ cell line. Notably, ICs CD73 and PD-L1 were closely associated with both CSC and EMT phenotypes. Knockdown of CD73 or PD-L1 reduced the proliferative and motile abilities of both adherent monolayers and anchorage-free spheroids. In conclusion, blocking CD73 and PD-L1 offer a promising therapeutic strategy for targeting highly aggressive populations with CSC and EMT phenotype to improve GBC patient prognosis.     

Granulated colloidal silicon dioxide-based self-microemulsifying tablets,as a versatile approach in enhancement of solubility and therapeutic potential of anti-diabetic agent: formulation design and in vitro/in vivo evaluation

The current research work was executed with an aim to explore and promote the potential of self-microemusifying drug delivery systems (SMEDDS) in the form of tablets, in order to enhance solubility and oral bioavailability of poorly aqueous soluble drug Repaglinide (RPG). RPG-loaded liquid SMEDDS were developed consisting Labrafil M 1944CS, Kolliphor EL and Propylene glycol, which were then characterized on various parameters. After characterization and optimization, liquid SMEDDS were converted into solid form by adsorbing on Aeroperl® 300 pharma and polyplasdone^TM XL. Further, selection of suitable excipients was done and mixed with prepared solidified SMEDDS powder followed by the preparation of self-microemulsifying tablets (SMET’s) wet granulation–compression method. SMET’s were subjected to differential scanning calorimetry (DSC) and particle X-ray diffraction (RXRD) studies, results of which indicated transformation of crystalline structure of RPG because of dispersion of RPG at molecular level in liquid SMEDDS. This was further assured by micrographs obtained from scanning electron microscope. SMET’s shown more than 85% (30?min) of in vitro drug release in contrast to conventional marketed tablets (13.2%) and pure RPG drug (3.2%). Results of in vivo studies furnished that SMET’s had shown marked decrease in the blood glucose level and prolonged duration of action (up to 8?h) in comparison with conventional marketed tablets and pure RPG drug. In conclusion, SMET’s serves as a promising tool for successful oral delivery of poorly aqueous soluble drug(s) such as RPG.     

Anti‐obesity effect of feeding probiotic dahi containing Lactobacillus casei NCDC 19 in high fat diet‐induced obese mice

Nowadays, studies about the anti‐obesity potential of probiotics are of growing interest. Lactobacilli are one of the well‐studied probiotics owing to their preventing effect on metabolic disorders. This study was undertaken to access the anti‐obesity effect of probiotic dahi containing Lactobacillus casei NCDC 19 on C57BL/6 mice. Feeding of probiotic dahi showed reduce body weight gain and epididymal fat weights. Moreover, blood glucose, plasma lipids and expression level of leptin were reduced and caecal bifidobacteria counts and adiponectin expression levels were significantly increased. It can be concluded that feeding of probiotic dahi containing L. casei NCDC 19 showed potential anti‐obesity effects.     

Lip as biometric and beyond: a survey

Owing to the recent fuel in investigation of lip as a biometrics trait both in physiological and behavioral aspect, and in healthcare application, it is imperative to comprehensively study and document the literature. Hence, in this work we enlist the works related to the lip as a biometirc trait and other applications-based on its behavior and physiology. Consequently, in this survey we first discuss the lip anatomy that permits to identify the physiological and behavioral properties. Followed by the list of challenges to characterize lip behavior and physiology. Next, we proceed to provide an insight of several inspiring ideas proposed in the literature to establish lip behavior and physiology for identity and other applications such as health monitoring and forensic. Whilst, it can be concluded at the end of the survey that their are several open research area and unsolved issues, which we discuss in details at the end of this survey to attract the attention of researchers.

     

DYNAMIC ENVIRONMENT ROBOT PATH PLANNING USING HIERARCHICAL EVOLUTIONARY ALGORITHMS

The problem of path planning deals with the computation of an optimal path of the robot, from source to destination, such that it does not collide with any obstacle on its path. In this article we solve the problem of path planning separately in two hierarchies. The coarser hierarchy finds the path in a static environment consisting of the entire robotic map. The resolution of the map is reduced for computational speedup. The finer hierarchy takes a section of the map and computes the path for both static and dynamic environments. Both the hierarchies make use of an evolutionary algorithm for planning. Both these hierarchies optimize as the robot travels in the map. The static environment path is increasingly optimized along with generations. Hence, an extra setup cost is not required like other evolutionary approaches. The finer hierarchy makes the robot easily escape from the moving obstacle, almost following the path shown by the coarser hierarchy. This hierarchy extrapolates the movements of the various objects by assuming them to be moving with same speed and direction. Experimentation was done in a variety of scenarios with static and mobile obstacles. In all cases the robot could optimally reach the goal. Further, the robot was able to escape from the sudden occurrence of obstacles.     

A technique for non-invasive application-level checkpointing

One of the key elements required for writing self-healing applications for distributed and dynamic computing environments is checkpointing. Checkpointing is a mechanism by which an application is made resilient to failures by storing its state periodically to the disk. The main goal of this research is to enable non-invasive reengineering of existing applications to insert Application-Level Checkpointing (ALC) mechanism. The Domain-Specific Language (DSL) developed in this research serves as a perfect means towards this end and is used for obtaining the ALC-specifications from the end-users. These specifications are used for generating and inserting the actual checkpointing code into the existing application. The performance of the application having the generated checkpointing code is comparable to the performance of the application in which the checkpointing code was inserted manually. With slight modifications, the DSL developed in this research can be used for specifying the ALC mechanism in several base languages (e.g., C/C++, Java, and FORTRAN).