Recently Cu-Al-Ni shape memory alloys have gained special attention due to their high temperature applications. This article attempts to formulate the various processing routes for processing of ...Cu-Al-Ni shape memory alloys such as casting route, powder metallurgy route, rapid solidification and spray forming process. The pros and cons of various processes are provided in detail. The additive manufacturing, which is an emerging process is discussed which could be a promising technique of preparing Cu-Al-Ni shape memory alloys. Further recommendations are provided in terms of producing fine-grained near net shape shape memory alloys for high temperature applications.
•Hot rolling of cast Cu-Al-Ni SMA after solution treatment exhibits weak properties due to large grain.•Rapid solidification process produces fine-grain but is not commercially viable.•Powder metallurgy route has potential to produce fine-grained with improved properties.•Few attempts are made on preparing Cu-Al-Ni SMA by spray deposition process producing equiaxed grains.•Selective laser melting is an emerging and promising technique for preparing Cu-Al-Ni SMA.
Display omitted
•Low density and highly porous nanofibrillated cellulose/PVA aerogel was fabricated.•Superhydrophobic modification was done by coating of stearic acid chloride solution.•NFC/PVA-SAC ...aerogel was very effective to clean oil/chemical spill.•Its efficiently of re-usability was proven by repeated uses by mechanical squeezing.
The present work aims towards the structuring of a physically cross-linked aerogels based on nanofibrillated cellulose (NFC) and polyvinyl alcohol (PVA), i.e., NFC/PVA aerogels for oil spillage cleanup. Highly porous (98%) NFC/PVA aerogels having both meso-micro pores were achieved by freeze drying technique. To impart super-hydrophobicity to the composite aerogel, a simple dip coating process was adopted using stearic acid chloride (SAC) solution. The SAC conjugated aerogels combined both superhydrophobic and oleophilic characteristics showed a contact angle of ∼159° and ∼0° with water and oil respectively. FESEM and X-ray microtomography images revealed a self-assembled 3D porous cellular structure of the aerogels. The prepared aerogels were found to be very efficient in separating a series of oil/water mixtures and various organic solvents with excellent selectivity and recyclability. Absorption capacity of the aerogels was at least 35 times higher than their dry weight. Simple mechanical squeezing method was adopted for repetitive uses.
Abstract Over the last two decades, berries and berry bioactives particularly anthocyanins and their aglycones anthocyanidins (Anthos) have demonstrated excellent anti-oxidant, anti-proliferative, ...apoptotic and anti-inflammatory properties. However, their physicochemical and pharmacokinetic limitations such as low solubility, low permeability, and poor oral bioavailability are considered as unfavorable properties for development as drugs. Therefore there is a need to develop systems for efficient systemic delivery and robust bioavailability. To overcome this barrier, in this study we prepared nano-formulation of bilberry-derived Anthos using exosomes harvested from raw bovine milk. Exosomal formulation of Anthos enhanced antiproliferative and anti-inflammatory effects compared with the free Anthos against various cancer cells in vitro . Our data also showed significantly enhanced therapeutic response of exosomal-Anthos formulation compared with the free Anthos against lung cancer tumor xenograft in nude mice. The Anthos showed no signs of gross or systemic toxicity in wild-type mice. Thus, exosomes provide an effective alternative for oral delivery of Anthos that is efficacious, cost-effective, and safe, and this regimen can be developed as a non-toxic, widely applicable therapeutic agent.
Gene-silencing with targeted siRNAs has great potential as a therapeutic approach for various diseases including cancer. However, intracellular delivery of siRNA is challenging. We used bovine milk ...exosomes as a novel system for siRNA delivery. First, we demonstrated that exosomes can deliver endogenous RNA payloads into recipient cells. Next, we loaded siRNA against specific genes including VEGF, EGFR, AKT, MAPK, and KRAS. We utilized 5′−32P-labeled siKRAS as a tracer and found exosome loading with siRNA could be variable. We demonstrated that the siRNA of loaded exosomes is stable and resist degradation. Our results indicated that siRNAs against target genes ranged from 2 to 10-fold knockdown in expression levels in various cancers. Since mutated KRAS has been implicated in the development of various cancers including lung cancer, we tested a mutant-allele specific siRNA against KRASG12S, in A549 cells. We observed a dose-dependent anti-proliferative activity against A549 cells treated with exosomes carrying siKRASG12S. We observed significant inhibition of A549 tumor xenografts in animals treated with folic acid-functionalized exosomes carrying siKRAS. In summary, milk-derived exosomes represent a viable natural nano-carrier for the delivery of siRNA for therapeutic application against cancer.
Display omitted
•Milk exosomes represent a viable natural nano-carrier for the delivery of siRNA.•Exosomes were loaded with siRNA using a chemical transfecting reagent, Exo-Fect.•siRNA loaded exosomes demonstrated 2–10-fold knockdown.•Exosome carrying siKRAS showed dose-dependent antiproliferative activity.•Folic acid-functionalized Exo-siKRAS significantly inhibited lung tumor xenograft.
Display omitted
The goal of the study was to fabricate folic acid functionalized docetaxel (DOC)/erlotinib (ERL)-loaded solid lipid nanoparticles (SLNs) to synergistically increase the anticancer ...activity against triple-negative breast cancer. DOC/ERL-SLNs were prepared by the high shear homogenization – ultrasound dispersion method (0.1 % w/v for DOC, and 0.3 %w/v for ERL) and optimized using Plackett Burman Design (PBD) followed by Box Behnken Design (BBD). The optimized SLNs demonstrated particle size < 200 nm, PDI < 0.35, and negative zeta potential with entrapment and loading efficiency of ∼80 and ∼4 %, respectively. The SLNs and folic acid functionalized SLNs (FA-SLNs) showed sustained release for both drugs, followed by Higuchi and Korsemeyer-Peppas drug release models, respectively. Further, the in vitro pH-stat lipolysis model demonstrated an approximately 3-fold increase in the bioaccessibility of drugs from SLNs compared to suspension. The TEM images revealed the spherical morphology of the SLNs. DOC/ERL loaded SLNs showed dose- and time-dependent cytotoxicity and exhibited a synergism at a molar ratio of 1:3 in TNBC with a combination index of 0.35 and 0.37, respectively. FA-DOC/ERL-SLNs showed enhanced anticancer activity as evidenced by MMP and ROS assay and further inhibited the colony-forming ability and the migration capacity of TNBC cells. Conclusively, the study has shown that SLNs are encouraging systems to improve the pharmaceutical attributes of poorly bioavailable drugs.
We have developed a synchrotron-based in situ X-ray micro-tomography facility for 3D imaging of material deformation under compression and tensile loads. In this report, we have discussed the details ...of this experimental facility, and as a case study, the quasi-static, elasto-plastic compression behavior of open-cell aluminum (Al) alloy foam is studied under in situ load conditions. Micro-tomography images obtained at different levels of compressive strains reveal damage kinetics of the cellular microstructure, observed in the form of strut bending and fracture, cell size reduction, shape distortion, cell wall collapse, etc. These morphological and structural changes are found to be closely correlated with specific variations in the stress–strain curve, which explain its macroscopic deformation behavior. The experimental stress–strain behavior is compared to a constitutive model for metal foams, and observed deviations are discussed for structure–property relations.
Abstract In this report milk-derived exosomes have been investigated for oral delivery of the chemotherapeutic drug paclitaxel (PAC) as an alternative to conventional i.v. therapy for improved ...efficacy and reduced toxicity. PAC-loaded exosomes (ExoPAC) were found to have a particle size of ~108 nm, a narrow particle size distribution (PDI ~0.190), zeta potential (~ −7 mV) and a practical loading efficiency of ~8%. Exosomes and ExoPAC exhibited excellent stability in the presence of simulated-gastrointestinal fluids, and during the storage at −80 °C. A sustained release of PAC was also observed up to 48 h in vitro using PBS (pH 6.8). Importantly, ExoPAC delivered orally showed significant tumor growth inhibition (60%; p < 0.001) against human lung tumor xenografts in nude mice. Treatment with i.p. PAC at the same dose as ExoPAC, however, showed modest but statistically insignificant inhibition (31%). Moreover, ExoPAC demonstrated remarkably lower systemic and immunogenic toxicities as compared to i.v. PAC.
Pathological biomineralization in the urinary system leads to urolithiasis. Formation of kidney stones involves a series of events during which they undergo morphological and mineralogical changes. ...We investigated the mineralization of biogenic struvite (in vitro) and examined the transformation of distinct interior and exterior structure of struvite. In vitro crystallization of struvite was performed in the presence of two bacteria that were originally isolated from the kidney stone patients. Morphological evaluation was carried out using SR-μCT as well as FESEM, XRD and FT-IR. Characteristic internal 3-D morphology and porosity of the stones were studied. For comparison, patient derived struvite stones were used. From the results obtained, we report that the presence of bacteria enhances the crystallization process of struvite in vitro. A series of time-resolved experiments revealed that struvite crystals experienced a significant morphologic evolution from pin pointed structure to X-shaped and tabular morphologies. These X-shaped and unusual tabular habits of struvite resembled biogenic morphologies of struvite. SR-μCT showed similarities between the patient derived and the in vitro derived struvite crystals. In conclusion, these experiments revealed that the bacteria play a major role in the specific morphogenesis of struvite and can able to control the nucleation, modulate crystalline phases, and shape of the growing crystal.
Abstract The present study was designed with the objective to investigate the stability and potential of glucomannan-modified bilosomes (GM-bilosomes) in eliciting immune response following oral ...administration. GM-bilosomes exhibited desired quality attributes simultaneously maintaining the chemical and conformation stability of the tetanus toxoid (TT) entrapped in to freeze dried formulations. The GM-bilosomes exhibited excellent stability in different simulated biological fluids and sustained release profile up to 24 h. GM-bilosomes elicited significantly higher ( P < 0.05) systemic immune response (serum IgG level) as compared to bilosomes, niosomes and alum adsorbed TT administered through oral route. More importantly, GM-bilosomes were found capable of inducing mucosal immune response, i.e. sIgA titre in salivary and intestinal secretions as well as cell mediated immune response (IL-2 and IFN-γ levels in spleen homogenate) which was not induced by i.m. TT, the conventional route of immunization. Conclusively, GM-bilosomes could be considered as a promising carrier and adjuvant system for oral mucosal immunization. From the Clinical Editor This team reports on the development and effects of a glucomannan-modified bilosome as an oral vaccine vector, using tetanus toxoid in the experiments. These GM-bilosomes not only elicited significantly higher systemic immune response as compared to bilosomes, niosomes and alum adsorbed orally administered TT, but also demonstrated mucosal immune response induction as well as cell mediated immune responses, which were not induced by the conventional route of immunization.
Understanding the mechanisms of kidney stone formation, development patterns and associated pathological features are gaining importance due to an increase in the prevalence of the disease and ...diversity in the presentation of the stone composition. Based on the microstructural characteristics of kidney stones, it may be possible to explain the differences in the pathogenesis of pure and mixed types of stones. In this study, the microstructure and distribution of mineral components of kidney stones of different mineralogy (pure and mixed types) were analyzed. The intact stones removed from patients were investigated using synchrotron radiation X-ray computed microtomography (SR-μCT) and the tomography slice images were reconstructed representing the density and structure distribution at various elevation planes. Infrared (IR) spectroscopes, X-ray diffraction (XRD) and scanning electron microscopy (SEM) were used to confirm the bulk mineral composition in the thin section stones. Observations revealed differences in the micro-morphology of the kidney stones with similar composition in the internal 3-D structure. Calcium oxalate monohydrate stones showed well-organised layering patterns, while uric acid stones showed lower absorption signals with homogenous inner structure. Distinct mineral phases in the mixed types were identified based on the differential absorption rates. The 3-D quantitative analysis of internal porosity and spatial variation between nine different types of stones were compared. The diversity among the microstructure of similar and different types of stones shows that the stone formation is complex and may be governed by both physiological and micro-environmental factors. These factors may predispose a few towards crystal aggregation and stone growth, while, in others the crystals may not establish stable attachment and/or growth.
PDF
