Development and Characterization of Lamivudine Loaded Nanoparticles.

Most of the drugs introduced to clinical medicine exert their effects by interactive interference with cell and cell membrane related structure and functions through concentration dependent reversible interactions at specific receptor site(s). Obviously, to obtain a desirable therapeutic response, the correct amount of drug should be transported and delivered to the site of action with subsequent control of drug input rate. The distribution of other tissues therefore seems unnecessary, wasteful and a potential cause of toxicity. The developments of over past decades indicate explicit progress in the area of controlled and targeted drug delivery. The present study Lamivudine nanoparticles aimed to develop a nanoparticulate drug delivery system of antiviral drug Lamivudine using biodegradable polymer Eudragit RS 100 & RL 100. The polymer enhances the binding of Lamivudine nanoparticles in specific or targeted site with sustained release of drug increasing therapeutic efficacy. These nanoparticles may also reduce the dose & dose frequency with desired therapeutic response. The pre-formulation studies were performed by using FTIR. The spectra of pure drug, pure polymer and nanoparticle formulation were examined. The study revealed the absence of significant interactions between drug and polymer. All batch of nanoparticles (F1-F10) were prepared by emulsion solvent evaporation method, formulation was subjected to evaluation involving following tests they are; Entrapment efficiency, In vitro drug release studies, Microscopic determination, Particle size determination, Sterility test and Stability test. The entrapment efficiency of the optimized formulation was 94 ± 0.05% andinvitro drug release was 92.89% after 24 hours. It also obeys the zero order,follows diffusion and erosion mechanism of release. Particle size determination by Scanning Electron Microscope shows the best formulation containing size of about 100 nm.The formulation passed the sterility test performed as per specifications of Indian pharmacopoeia. The stability test performed revealed that the formulation was good. The best formulation was examined for zeta potential determinations. The formulation (F9) showed maximum deviation of -27mV which demonstrated that the particles are separate and highly repelling. This repelling property found to be more useful in decreasing opsonization and favors target specificity. The prepared formulation was sterilized by Membrane filtration technique. It was an aseptic technique involving the use of laminar air flow workstation

DELAMINATION PREDICTION IN DRILLING OF CFRP COMPOSITES USING ARTIFICIAL NEURAL NETWORK

Carbon fibre reinforced plastic (CFRP) materials play a major role in the applications of aeronautic, aerospace, sporting and transportation industries. Machining is indispensible and hence drilling of CFRP materials is considered in this present study with respect to spindle speed in rpm, drill size in mm and feed in mm/min. Delamination is one of the major defects to be dealt with. The experiments are carried out using computer numerical control machine and the results are applied to an artificial neural network (ANN) for the prediction of delamination factor at the exit plane of the CFRP material. It is found that ANN model predicts the delamination for any given set of machining parameters with a maximum error of 0.81% and a minimum error of 0.03%. Thus an ANN model is highly suitable for the prediction of delamination in CFRP materials

Experimental Studies on Abrasive Water Jet Cutting of Nano SiC Particles Filled Hybrid Basalt-Glass Fibre-Reinforced Epoxy Composites

Abrasive water jet machining (AWJM) is extensively beneficial in machining materials that are hard to cut. This investigation deals with AWJM of Nano SiC filled Epoxy reinforced with basalt-glass fiber hybrid composite. The composite is prepared by compression moulding technique. Experimental trails are performed to evaluate the impact of every process parameter on the responses i.e., surface roughness (Ra) and Material Removal Rate (MRR). The experiments are conducted by changing the standoff distance (SD), traverse speed (TS) and water pressure. The performance of the conducted experiment is analysed using a Swarm intelligence algorithm. Surface roughness and MRR are maximized by using the combination of optimum process parameter levels of 9.72 mm/min speed, 5.78 mm stand-off distance and 553 MPa jet pressure. Scanning Electron Microscopic (SEM) images are employed in detecting the morphology of machined surface and confirmed the presence of voids and fibre pull-out

Investigation on the Turning Parameters for Surface Roughness using Taguchi Analysis

One of the important interests in the machining is attaining better surface roughness as well as dimensional accuracy. Polymer materials are continuously displacing the conventional materials. Their machining behavior is different in many aspects from machining of conventional metallic materials. Polymer based composite materials have superior properties for mechanical strength and stiffness, such as high strength-to-weight ratio and high stiffness-to-weight ratio. Fiber reinforced polymer composite materials are the one which are produced closer to the required shape, further machining is often necessary to achieve expected surface characteristics. This experimental study targets the machining of carbon fiber reinforced polymer material made into the form of tube. It examines various process parameters such as cutting speed, feed and depth of cut and their importance in deciding the surface roughness. Surface roughness was measured after machining is carried out under specified machining conditions. This experimental study focuses on the prediction of machining parameters that yield better surface characteristics in order to avoid machining of hard materials such as fiber reinforced composite materials so that enormous money spent in machining could be saved to some extent. For prediction this experimental study makes use of response surface methodology. The Taguchi method is used to solve many engineering problems. This work uses the Taguchi's orthogonal array method to find out the number of experiments to be carried out for turning operations. Also the analysis of variance is used to investigate the cutting parameters. In addition to the optimal cutting parameters for turning operations, the main cutting parameter that affect the cutting performance in turning operations could be found out

Prospects of friction stir processed Mg alloys and composites-Reviews and suggestions

The pursuit of advanced materials with enhanced or tailored properties has indeed been a crucial focus in various industries. From aerospace to automotive, and from nuclear power to space exploration, the need for materials that can withstand extreme conditions, offer improved performance, and ensure safety is paramount. Safety standards are vital in industries where materials are subjected to extreme conditions or where failure could have catastrophic consequences. Therefore, research in advanced materials not only focuses on enhancing properties but also ensuring that these materials meet rigorous safety standards. Friction stir processing (FSP) emerges as a transformative methodology, facilitating the achievement of superplasticity, enhanced ductility, heightened strength, toughness, and hardness, all while preserving the structural integrity of the material. In recent years, notable advancements have been witnessed in preparing magnesium (Mg) alloys, Mg composites, and functional Mg materials. This comprehensive review encompasses the latest developments, global significance, adherence to standards, and innovative strides in Mg alloys from 2011 to 2023. It includes the FSP processing techniques, governing mechanism, advantageous properties, grain size, dislocations and their impacts, corrosion, wear behaviour, formability studies, cryogenic FSP, underwater FSP and friction stir additive manufacturing. Readers will gain critical insights, receive constructive suggestions, and discern future directions from this extensive review, as it encapsulates the trajectory of advancements in Mg alloys and delineates promising horizons with potentially transformative impacts in materials science research. Prospects and potential areas would deem help upcoming researchers to pursue with new advanced materials

Cloaking nanoparticles with protein corona shield for targeted drug delivery

Targeted drug delivery using nanoparticles can minimize the side effects of conventional pharmaceutical agents and enhance their efficacy. However, translating nanoparticle-based agents into clinical applications still remains a challenge due to the difficulty in regulating interactions on the interfaces between nanoparticles and biological systems. Here, we present a targeting strategy for nanoparticles incorporated with a supramolecularly pre-coated recombinant fusion protein in which HER2-binding affibody combines with glutathione-S-transferase. Once thermodynamically stabilized in preferred orientations on the nanoparticles, the adsorbed fusion proteins as a corona minimize interactions with serum proteins to prevent the clearance of nanoparticles by macrophages, while ensuring systematic targeting functions in vitro and in vivo. This study provides insight into the use of the supramolecularly built protein corona shield as a targeting agent through regulating the interfaces between nanoparticles and biological systems

Protein mimetic amyloid inhibitor potently abrogates cancer-associated mutant p53 aggregation and restores tumor suppressor function

Missense mutations in p53 are severely deleterious and occur in over 50% of all human cancers. The majority of these mutations are located in the inherently unstable DNA-binding domain (DBD), many of which destabilize the domain further and expose its aggregation-prone hydrophobic core, prompting self-assembly of mutant p53 into inactive cytosolic amyloid-like aggregates. Screening an oligopyridylamide library, previously shown to inhibit amyloid formation associated with Alzheimer\u2019s disease and type II diabetes, identified a tripyridylamide, ADH-6, that abrogates self-assembly of the aggregation-nucleating subdomain of mutant p53 DBD. Moreover, ADH-6 targets and dissociates mutant p53 aggregates in human cancer cells, which restores p53\u2019s transcriptional activity, leading to cell cycle arrest and apoptosis. Notably, ADH-6 treatment effectively shrinks xenografts harboring mutant p53, while exhibiting no toxicity to healthy tissue, thereby substantially prolonging survival. This study demonstrates the successful application of a bona fide small-molecule amyloid inhibitor as a potent\ua0anticancer agent

Metabolic adaptation drives arsenic trioxide resistance in acute promyelocytic leukemia.

Acquired genetic mutations can confer resistance to arsenic trioxide (ATO) in the treatment of acute promyelocytic leukemia (APL). However, such resistance-conferring mutations are rare and do not explain most disease recurrence seen in the clinic. We have generated stable ATO-resistant promyelocytic cell lines that are also less sensitive to ATRA and the combination of ATO and ATRA compared to the sensitive cell line. Characterization of these in-house generated resistant cell lines showed significant differences in immunophenotype, drug transporter expression, anti-apoptotic protein dependence, and PML-RARA mutation. Gene expression profiling revealed prominent dysregulation of the cellular metabolic pathways in these ATO resistant APL cell lines. Glycolytic inhibition by 2-DG was sufficient and comparable to the standard of care (ATO) in targeting the sensitive APL cell line. 2-DG was also effective in the in vivo transplantable APL mouse model; however, it did not affect the ATO resistant cell lines. In contrast, the resistant cell lines were significantly affected by compounds targeting the mitochondrial respiration when combined with ATO, irrespective of the ATO resistance-conferring genetic mutations or the pattern of their anti-apoptotic protein dependency. Our data demonstrate that the addition of mitocans in combination with ATO can overcome ATO resistance. We further show that this combination has the potential in the treatment of non-M3 AML and relapsed APL. The translation of this approach in the clinic needs to be explored further

Systemic Biomarkers of Neutrophilic Inflammation, Tissue Injury and Repair in COPD Patients with Differing Levels of Disease Severity

The identification and validation of biomarkers to support the assessment of novel therapeutics for COPD continues to be an important area of research. The aim of the current study was to identify systemic protein biomarkers correlated with measures of COPD severity, as well as specific protein signatures associated with comorbidities such as metabolic syndrome. 142 protein analytes were measured in serum of 140 patients with stable COPD, 15 smokers without COPD and 30 non-smoking controls. Seven analytes (sRAGE, EN-RAGE, NGAL, Fibrinogen, MPO, TGF-α and HB-EGF) showed significant differences between severe/very severe COPD, mild/moderate COPD, smoking and non-smoking control groups. Within the COPD subjects, univariate and multivariate analyses identified analytes significantly associated with FEV1, FEV1/FVC and DLCO. Most notably, a set of 5 analytes (HB-EGF, Fibrinogen, MCP-4, sRAGE and Sortilin) predicted 21% of the variability in DLCO values. To determine common functions/pathways, analytes were clustered in a correlation network by similarity of expression profile. While analytes related to neutrophil function (EN-RAGE, NGAL, MPO) grouped together to form a cluster associated with FEV1 related parameters, analytes related to the EGFR pathway (HB-EGF, TGF-α) formed another cluster associated with both DLCO and FEV1 related parameters. Associations of Fibrinogen with DLCO and MPO with FEV1/FVC were stronger in patients without metabolic syndrome (r  =  −0.52, p  = 0.005 and r  =  −0.61, p  = 0.023, respectively) compared to patients with coexisting metabolic syndrome (r  =  −0.25, p  = 0.47 and r  =  −0.15, p  = 0.96, respectively), and may be driving overall associations in the general cohort. In summary, our study has identified known and novel serum protein biomarkers and has demonstrated specific associations with COPD disease severity, FEV1, FEV1/FVC and DLCO. These data highlight systemic inflammatory pathways, neutrophil activation and epithelial tissue injury/repair processes as key pathways associated with COPD