Formulation Composition Research Articles

Dry granulation of vitamin D3 and iron in corn starch matrix: Powder flow and structural properties

In this work, a twin-screw dry granulation (TSDG) was adopted to produce vitamin D3 (VD3) and iron blended dry granules using corn starch as an excipient. Response surface methodology was applied to determine the effect of the formulation compositions (VD3 and iron) on granule properties [tapped bulk density, oil holding capacity, and volumetric mean particle size (Dv50)]. Results indicated that the model fitted well, and responses, in particular flow properties, were significantly affected by the composition. The Dv50 was only influenced by the addition of VD3. The flow properties were characterized by the Carr index and Hausner ratio, which indicated very poor flow of the granules. Scanning electron microscopy with energy dispersive spectroscopy confirm the presence and distribution of Fe++ and VD3 in the granules. Overall, TSDG was proven to be a simple alternative method for the preparation of dry granules of VD3 and iron in a blend.

Enhancing the biopharmaceutical attributes of atorvastatin calcium using polymeric and lipid-polymer hybrid nanoparticles: An approach for atherosclerosis treatment

Atherosclerosis is associated with inflammation in the arteries, a significant cause of heart attacks and strokes. Although statin therapy can reduce the chances of atherosclerotic plaque formation, they need to be administered in high doses due to low systemic bioavailability and encountered with side effects. To overcome these challenges, we developed nanoparticles using biocompatible and biodegradable lipids and polymers for improving systemic drug absorption and therapeutic response. The polymeric nanoparticles were prepared using PLGA and PVA, while hybrid nanoparticles were prepared using PLGA and Phospholipon 90 G. Both nanoparticles were systematically optimized by I-optimal response surface design. The optimum formulation composition exhibited particle size of less than 250 nm, polydispersity index of less than 0.3, entrapment efficiency of more than 70%, and sustained drug release up to 6 h. In vivo pharmacokinetic evaluation in rats indicated multi-fold improvement in the extent of drug absorption (Cmax and AUCtotal) for atorvastatin from the nanoparticles vis-à-vis the pure drug suspension. In vivo pharmacodynamic studies also indicated the excellent ability of nanoparticles to lower the elevated levels of lipids (total cholesterol, triglycerides, and low-density lipoproteins) and increase the level of high-density lipoproteins as compared to that of the pure drug suspension.

Processing methods for conductive polymer composite bipolar plates: Effect on plate quality and performance

AbstractConductive polymer composites (CPCs) have been identified as viable replacements for graphite and metals for polymer electrolyte membrane fuel cell (PEMFC) bipolar plates (BPs). One important factor, apart from composite formulation, that affects the quality and properties of CPC BPs is the processing route. Therefore, understanding the possible processing methods for different matrix–filler combinations and their effects on the quality and properties of the plates can help in controlling and improving the final performance of BPs. This paper reviews the blending and molding techniques for CPC BPs, with a focus on relationship between formulation and processing method. The effects of processing route and conditions on microstructural features of CPC BPs, which affect the performance of the plates are also discussed. Finally, directions for further studies with potential to advance the development of quality and high‐performance CPC BPs are highlighted. Identified key areas for further research include control of filler orientation to improve through‐plane conductivity, correlation between processing parameters and dimensional accuracy of molded plates, and additive manufacturing of composite BPs.

Machine learning using multi-modal data predicts the production of selective laser sintered 3D printed drug products

Three-dimensional (3D) printing is drastically redefining medicine production, offering digital precision and personalized design opportunities. One emerging 3D printing technology is selective laser sintering (SLS), which is garnering attention for its high precision, and compatibility with a wide range of pharmaceutical materials, including low-solubility compounds. However, the full potential of SLS for medicines is yet to be realized, requiring expertise and considerable time-consuming and resource-intensive trial-and-error research. Machine learning (ML), a subset of artificial intelligence, is an in silico tool that is accomplishing remarkable breakthroughs in several sectors for its ability to make highly accurate predictions. Therefore, the present study harnessed ML to predict the printability of SLS formulations. Using a dataset of 170 formulations from 78 materials, ML models were developed from inputs that included the formulation composition and characterization data retrieved from Fourier-transformed infrared spectroscopy (FT-IR), X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC). Multiple ML models were explored, including supervised and unsupervised approaches. The results revealed that ML can achieve high accuracies, by using the formulation composition leading to a maximum F1 score of 81.9%. Using the FT-IR, XRPD and DSC data as inputs resulted in an F1 score of 84.2%, 81.3%, and 80.1%, respectively. A subsequent ML pipeline was built to combine the predictions from FT-IR, XRPD and DSC into one consensus model, where the F1 score was found to further increase to 88.9%. Therefore, it was determined for the first time that ML predictions of 3D printability benefit from multi-modal data, combining numeric, spectral, thermogram and diffraction data. The study lays the groundwork for leveraging existing characterization data for developing high-performing computational models to accelerate formulation development.

Internal Explosion Performance of RDX@Nano-B Composite Explosives.

Boron powder is an additive for metalized explosives with great application potential. To improve the energy release ability of boron powder, the composites of RDX and nano-boron (RDX@Nano-B) were prepared by the spray-drying process, and the metalized explosives based on it were designed (named PBX-B1). The detonation heat and explosion pressure of boron-containing explosives PBX-B1 under vacuum and air conditions were measured and analyzed by an internal explosion test. On the other hand, the equilibrium pressure and energy release of the PBX-B1 explosive system after detonation were analyzed and compared with that of an explosive formulation of the same composition (named PBX-B2). Results showed that the detonation heat of PBX-B1 was 7456 J/g in a vacuum environment, which was 34.8% higher than that of RDX (5530 J/g). However, in the air environment, the detonation heat of PBX-B1 increased by 19.2% compared with that in the vacuum environment, and the explosive gas products mainly included N2, NOx, CO, H2O, CH4, HCN, and CO2. The peak pressure and equilibrium pressures of PBX-B1 were 11.2 and 0.42 MPa, which were increased by 155% and 75% compared with the vacuum environment, respectively. It is worth noting that, compared with that of PBX-B2, the released energy in the aerobic combustion stage and equilibrium pressure of PBX-B1 were increased by 49.8% and 10.5%. This study demonstrated the strategy of improving the energy release of boron-containing metalized explosives through the design of an explosive microstructure, which provides important clues for the design of higher-energy metalized explosives.

State of the art on the hydraulic properties of pervious concrete

Pervious concrete is a type of concrete with high porosity that allows water to pass through it. It has a range of environmental benefits, including stormwater management, noise reduction, and temperature regulation. However, testing the permeability and strength of pervious concrete is costly and time-consuming, due to the many variables that can influence these properties. This paper presents research on the factors that influence the porosity and permeability of pervious concrete, including the type and size of aggregates, the water-cement ratio, and the cement-paste content. The paper also compares different methods of measuring permeability, and finds that a constant-head permeameter is more accurate than a falling-head permeameter. Additionally, the study investigates the clogging of pervious concrete and strategies to prevent it. The results of this research aim to improve the design of pervious concrete for use in the urban built environment. Highlights This paper presents the composition and method of formulation of pervious concrete based on cement and natural aggregates. Factors affecting the porosity of pervious concrete are identified. Correlations are established between the permeability and open porosity of pervious concrete. Factors influencing the permeability of pervious concrete are studied. Methods of measuring permeability are presented, and the results obtained with these different methods are compared. Different models for predicting the permeability of pervious concrete are presented.

Rational Optimization of Cathode Composites for Sulfide-Based All-Solid-State Batteries

All-solid-state lithium-ion batteries with argyrodite solid electrolytes have been developed to attain high conductivities of 10-3 S cm-1 in studies aiming at fast ionic conductivity of electrolytes. However, no matter how high the ionic conductivity of the electrolyte, the design of the cathode composite is often the bottleneck for high performance. Thus, optimization of the composite cathode formulation is of utmost importance. Unfortunately, many reports limit their studies to only a few parameters of the whole electrode formulation. In addition, different measurement setups and testing conditions employed for all-solid-state batteries make a comparison of results from mutually independent studies quite difficult. Therefore, a detailed investigation on different key parameters for preparation of cathodes employed in all-solid-state batteries is presented here. Employing a rational approach for optimization of composite cathodes using solid sulfide electrolytes elucidated the influence of different parameters on the cycling performance. First, powder electrodes made without binders are investigated to optimize several parameters, including the active materials' particle morphology, the nature and amount of the conductive additive, the particle size of the solid electrolyte, as well as the active material-to-solid electrolyte ratio. Finally, cast electrodes are examined to determine the influence of a binder on cycling performance.

An anode-free aqueous hybrid batteries enabled by in-situ Cu/Sn/Zn alloy formation on pure Cu substrate

Zn-based rechargeable aqueous battery attracts attention due to its simplicity and benignity. Here, we propose an anode-free aqueous hybrid system with 4 M ZnSO4 and 2 M Li2SO4 in 10% DME. Since the electrolyte is the only source of Zn, the capacity ratio between Zn salts and the cathode is also evaluated to achieve a suitable formulation of the electrolyte composition. To improve the Zn nucleation and densify the deposition, we include an additive SnBr2 to initiate the in-situ formation of Cu/Sn/Zn alloy on the surface of the Cu current collector. The effects of the SnBr2 additive on the Zn deposition, stripping, and the Cu/Sn/Zn alloy formation was investigated and characterized. SEM, cross-sectional analysis by Focused ion beam (FIB), and in-situ transmission X-ray microscope (TXM) all confirm the more uniform and dense deposition of Zn on Cu under the assistance of SnBr2. The anode-free hybrid aqueous Cu||LFP full cell achieves 99.1% average coulombic efficiency with relatively good capacity retention (35.2%) after 100 cycles by adding SnBr2 in the hybrid electrolyte with an optimized electrolyte/cathode capacity ratio of 9.45. The proposed anode-free approach is hoped to help the sustainable development of an aqueous battery system with high energy density and environmental benignity.

Sublimation of Drugs from the Site of Application of Topical Products.

The objective of the project was to investigate the plausibility of active pharmaceutical ingredients (APIs) to undergo sublimation from topical application following evaporation of solvent. Topical formulations with different APIs were subjected to a sublimation screening test. The APIs in the selected topical products were found to undergo sublimation to a different extent. The salicylic acid topical product was found to undergo a significant loss due to sublimation. The extent of sublimation of salicylic acid was significantly greater at skin temperature compared to room temperature. When the APIs were subjected to the sublimation screening test in their neat form at 32 ± 1 °C, the natural log of the rate of sublimation decreased linearly with the standard enthalpy of sublimation of compound (R2 = 0.89). The formulation composition was found to have a significant impact on the extent of sublimation of the representative API, salicylic acid. The sublimation of APIs from the topical product was found to affect the mass balance studies in the case of the salicylic acid ointment. Furthermore, the results of the human studies agreed with the in vitro experimental results demonstrating the plausibility of loss of API due to sublimation from the site of application.

Formulation of a Simulated Wastewater Influent Composition for Use in the Research of Technologies for Managing Wastewaters Generated during Manned Long-Term Space Exploration and Other Similar Situations—Literature-Based Composition Development

The prospect of humans inhabiting planetary bodies is gaining interest among research and development communities, with the moon being considered as a transitory base camp and Mars the next planet humans will inhabit. NASA's Mission to Mars program is set to have humans inhabiting Mars within on-planet space camps by the Year 2030, which has tremendously increased research and development for space exploration-including research oriented toward human life support in long-term planetary lodging camps. The sustenance of human life on Mars will not be trivial due to the unavailability of an appropriate atmosphere and usable water. This situation requires a self-sustaining human life support system that can provide the basic needs such are breathable air, potable water, food, and energy. The feasibility of sending a payload with resources adequate to support long-term human inhabitation is not reasonable, which means every resource within a Mars space camp is valuable, including human-produced wastes. A biorefinery system that treats wastewater and can also produce valuable products such as oxygen, food, and energy offers a form of circular utilization of valuable resources. To conduct research for such systems requires a wastewater influent that is representative of the wastewater to be generated by the space crew within this isolated, confined environment, which is different from what is generated on Earth due to limited variability in diet, human activity, and lifestyle in this confined area. Collection of actual wastewater influent from an isolated environment supporting humans is challenging. Additionally, to ensure a safe working environment in the laboratory and avoid the imposed threat of handling actual human feces, the proposed synthetic, non-human feces containing wastewater influent formulation offers an easy-to-produce and safer-to-handle option. This paper reviews several synthetic wastewater compositions that have been formulated for space exploration purposes. None of the formulations were found to be realistic nor adequate for a space-camp-type scenario. Thus, the formulation of a synthetic wastewater for simulating a wastewater influent from a human space-based camp is proposed in this paper. In addition, the physical, chemical, and biodegradation characteristics of the final formulation designed are presented to illustrate the value of the proposed influent formulation.

Sustainable Materials Containing Biochar Particles: A Review.

The conversion of polymer waste, food waste, and biomasses through thermochemical decomposition to fuels, syngas, and solid phase, named char/biochar particles, gives a second life to these waste materials, and this process has been widely investigated in the last two decades. The main thermochemical decomposition processes that have been explored are slow, fast, and flash pyrolysis, torrefaction, gasification, and hydrothermal liquefaction, which produce char/biochar particles that differ in their chemical and physical properties, i.e., their carbon-content, CHNOS compositions, porosity, and adsorption ability. Currently, the main proposed applications of the char/biochar particles are in the agricultural sector as fertilizers for soil retirement and water treatment, as well as use as high adsorption particles. Therefore, according to recently published papers, char/biochar particles could be successfully considered for the formulation of sustainable polymer and biopolymer-based composites. Additionally, in the last decade, these particles have also been proposed as suitable fillers for asphalts. Based on these findings, the current review gives a critical overview that highlights the advantages in using these novel particles as suitable additives and fillers, and at the same time, it shows some drawbacks in their use. Adding char/biochar particles in polymers and biopolymers significantly increases their elastic modulus, tensile strength, and flame and oxygen resistance, although composite ductility is significantly penalized. Unfortunately, due to the dark color of the char/biochar particles, all composites show brown-black coloration, and this issue limits the applications.

Ketorolac-Loaded PLGA-/PLA-Based Microparticles Stabilized by Hyaluronic Acid: Effects of Formulation Composition and Emulsification Technique on Particle Characteristics and Drug Release Behaviors.

This study aimed to develop ketorolac microparticles stabilized by hyaluronic acid based on poly(lactide-co-glycolide) (PLGA), poly(lactide) (PLA), and their blend for further application in osteoarthritis. The polymer blend may provide tailored drug release and improved physicochemical characteristics. The microparticles were prepared by water-in-oil-in-water (w/o/w) double emulsion solvent evaporation using two emulsification techniques, probe sonication (PS) and high-speed stirring (HSS), to obtain the microparticles in different size ranges. The results revealed that the polymer composition and emulsification technique influenced the ketorolac microparticle characteristics. The PS technique provided significantly at least 20 times smaller average size (1.3-2.2 µm) and broader size distribution (1.5-8.5) than HSS (45.5-67.4 µm and 1.0-1.4, respectively). The encapsulation efficiency was influenced by the polymer composition and the emulsification technique, especially in the PLA microparticles. The DSC and XRD results suggested that the drug was compatible with and molecularly dissolved in the polymer matrix. Furthermore, most of the drug molecules existed in an amorphous form, and some in any crystalline form. All of the microparticles had biphasic drug release composed of the burst release within the first 2 h and the sustained release over 35 days. The obtained microparticles showed promise for further use in the treatment of osteoarthritis.

The Influence on Fracture Resistance of Different Composite Resins and Prefabricated Posts to Restore Endodontically Treated Teeth.

Recent formulations of resin-based composites have incorporated different combinations of materials. However, the mechanical and bonding behavior of these materials with intraradicular posts are unclear. This study aimed to evaluate the effect of light-cure and dual-cure resin composite posts on the fracture resistance of endodontically-treated teeth. Materials and Methods: Ninety extracted human upper canines were selected and randomly divided into nine groups (n=10): (G1) endodontically treated teeth without endodontic posts; (G2) glass-fiber post cemented with glass-ionomer cement; (G3) endodontic post by dual-cure composite resin (Rebilda DC); (G4) endodontic post by dual-cure composite resin (Cosmecore); (G5) endodontic post by dual-cure composite resin (Bis-Core); (G6) endodontic post by light-cure composite resin; (G7) glass-fiber post customized with flowable composite resin; (G8) glass-fiber post cemented with light-cure composite resin; (G9) glass-fiber post cemented with self-adhesive resin cement. After the post insertion, all specimens were subjected to mechanical (250,000 cycles) and thermocycling (6000 cycles, 5 °C/55 °C) and immediate loading at 45 degrees in a universal testing machine until fracture. The data were analyzed by one-way ANOVA and multiple comparisons using the Fisher LSD Method (p < 0 05). Results: The mean failure loads (±SD) for the groups ranged from 100.7 ± 22.6 N to 221.9 ± 48.9 N. The G1 group (without endodontic posts) had a higher fracture strength than all experimental groups (p < 0.001). Conclusions: Within the limitations, the light- and dual-cure post technique did not present lower fracture resistance values as compared to the conventional glass-fiber post.

Microleakage and Marginal Integrity of Surface-Coated and Laser-Pretreated Class V Composite Restorations in Primary Teeth.

Introduction: Despite the advanced formulations of resin composites, microleakage is still among the commonest causes of clinical failure of these restorations. We evaluated the effect of surface coating and laser pretreatment on the microleakage of Class V resin composite restorations in primary teeth. Methods: Sixty extracted primary molar teeth having intact lingual or facial surfaces were randomly allocated into the control, G-Coat Plus surface coating, and erbium-doped yttrium aluminum garnet (Er:YAG) laser pretreatment groups. Class V cavities were provided with the coronal and gingival margins in the dentin and enamel, respectively. Restoration of the cavities was done with Z250 resin composite and they were thermocycled, followed by immersing in 2% basic Fuchsin dye for 24 hrs. Samples underwent sectioning occlusogingivally and the microleakage was assessed under a stereomicroscope (40×). Statistical analysis was done via SPSS and Kruskal-Wallis test (α=0.05). Results: The control and G-Coat plus groups were significantly different regarding the microleakage (P<0.001), and G-Coat Plus and laser pretreatment groups (P<0.001) at both gingival and occlusal margins. However, it showed no significant difference between the laser and the control group on the enamel (P=0.063) and dentin margins (P=0.757). Microleakage at the gingival margins was significantly greater compared to the occlusal margins in the control and laser groups (P<0.001), but not in the G-Coat Plus group (P=0.051). Conclusion: G-Coat plus coating significantly reduced microleakage at dentin and enamel margins of Class V composite restorations in primary teeth, in comparison with other groups of the study. Also, dentin margins showed more significant amounts of microleakage versus enamel margins in all groups, except for the G-Coat Plus group.

Исследования льдообразующих свойств кластеров из нанотрубок оксида цинка

Introduction. In recent years, the volume of funds used in the practice of weather modification has been growing in the world. Silver, the main component of weather modification funds, is a rather expensive metal. Therefore, the issue of reducing the silver content in the formulations of pyrotechnic compositions or the use of other effective ice-forming agents is relevant. Zinc oxide, like silver iodide, has ice-forming properties. When zinc is sublimated in water vapor, clusters of nanotubes of various sizes are formed. In this regard, experimental studies of the mechanism of ice formation on clusters of zinc oxide nanotubes seem to be an urgent task. The results of these studies are presented in this article. Materials and research methods. During thermal sublimation of reagents nanoscale particles are formed. These particles combine into clusters. The shape and size of these clusters, as well as their ice-forming properties, depend on the thermodynamic state of the medium in which they are formed. Tests of the ice-forming efficiency of such reagents should be carried out in conditions in clouds. This article presents the results of laboratory modeling of the formation of ice crystals during the interaction of zinc oxide clusters consisting of nanotubes, and the results of their comparison with the pyrotechnic composition AD–1 used in practice of weather modification, which is used in anti-hail products of the type «Alazan–6» and «Alazan–9» [1]. Research results and their discussion. The article presents the equipment and methods of performing experiments to study the ice-forming properties of clusters of zinc oxide nanotubes obtained in a cloud chamber during zinc sublimation in the presence of water vapor. The experiments were carried out on laboratory installations in the temperature range from –3 to –14 °C. The effectiveness of a reagent based on clusters of zinc oxide nanotubes has been investigated and compared with the effectiveness of the pyrotechnic composition of AD–1. The research results are presented in Tables 1–6 and Figures 2–7. Conclusions. In the course of laboratory experiments, a method for studying the ice-forming properties of clusters of zinc oxide nanotubes has been developed. When the pyrotechnic composition of AD–1 is sublimated, particles with a diameter from 20 nm to 400 nm with a modal value of 70 nm are formed. Zinc oxide clusters have a porous, loose structure, low density and larger sizes, almost two orders of magnitude larger than the sizes of silver iodide particles. Large ice crystals are formed on them. The total area of crystals formed on clusters of zinc oxide nanotubes is an order of magnitude larger than the total area of crystals formed on particles of the pyrotechnic composition AD–1. The reagent consisting of zinc oxide clusters is comparable in ice-forming characteristics to the pyrotechnic composition of AD–1 and can be recommended for practical use.

Особенности проведения ремонтновосстановительных работ в газовых скважинах месторождений Западной Сибири, находящихся на стадии падающей добычи

Introduction. The article discusses the features of carrying out repair and restoration work in gas wells of Western Siberian fields that are at the stage of declining production. The compositions of process fluids used to block the bottomhole formation zone during well killing, to isolate the inflow of formation waters in various mining and geological conditions are given. The compositions of process fluids used in repair and restoration work in certain fields of Western Siberia are presented. They are easily removed when inducing inflow from the formation, and allow providing the required pressure at the bottomhole, as well as maintaining the reservoir properties of the productive formation and preventing its destruction. Materials and research methods. Based on the generalization of field experience in killing wells, fields at the stage of declining production, the results of their own theoretical, laboratory and bench studies. Research results and their discussion. When killing wells with temporary blocking of the bottomhole formation zone, the choice of the composition of process fluids with high stability, low filtration, in a wide range of adjustable density and rheological properties, allows creating the necessary repression on the formation and carrying out various operations in the well without complications. Technological fluids for killing wells, which are direct-type emulsion systems based on a composite reagent, are pseudo-plastic systems in terms of rheological parameters, where the density range is 900-1000 kg/m3. The properties of the emulsion solution based on the kill fluid reagent are determined by the complex effect of the reagents included in its composition. Filler-based blocking fluids are used to temporarily block the bottomhole formation zone of wells, and are prepared by introducing the calculated amount of the reagent into the required volume of killing fluid based on the killing fluid reagent. As a water-insulating composition for creating an insulating barrier in the reservoir, a formulation of a gel-forming composition based on a reagent – a dry mixture for carrying out repair and restoration work and a gelforming reagent – is considered. Conclusions. Based on the study, it was determined that the most promising technology for killing wells under conditions of abnormally low formation pressures is the technology of preliminary blocking of the bottomhole formation zone using blocking fluids with filler. To ensure high efficiency of repair and restoration work, preliminary calculations of the process fluids used are necessary, taking into account the mining and geological conditions of the reservoir and the geometric parameters of the well.

The role of Eudragit® as a component of hydrogel formulations for medical devices.

Over the last decade, significant progress has been made in developing hydrogels as medical devices. By physically cross-linking pharmaceutically approved polymers into three-dimensional matrices, we can ensure their biocompatibility and facilitate their seamless transition from the laboratory to clinical applications. Moreover, the reversible nature of their physical cross-links allows hydrogels to dissolve in the presence of external stimuli. Particularly, their high degree of hydration, high molecular weight, and superior flexibility of the polymer chains facilitate their interaction with complex biological barriers (e.g., mucus layer), making them ideal candidates for mucosal drug delivery. However, fine-tuning the composition of the hydrogel formulations is of great importance to optimize the performance of the medical device and its therapeutic cargo. Herein, we investigated the influence of different Eudragits® on the properties of hydrogels based on polyvinylpyrrolidone (PVP), polyvinyl alcohol (PVA), and polyethylene glycol (PEG), which were originally proposed as ocular inserts in previous reports. Our research aims to determine the effects that including different Eudragits® have on the structure and protein ocular delivery ability of various hydrogel formulations. Properties such as matrix stability, protein encapsulation, release kinetics, mucoadhesion, and biocompatibility have been analyzed in detail. Our study represents a guideline of the features that Eudragits® have to exhibit to endow hydrogels with good adhesion to the eye's conjunctiva, biocompatibility, and structural strength to cope with the ocular biointerface and allow sustained protein release. This work has important implications for the design of new hydrogel materials containing Eudragits® in their composition, particularly in mucosal drug delivery.

Influence of electrode processing and electrolyte composition on multiwall carbon nanotube negative electrodes for sodium ion batteries

Nanostructured one-dimensional multiwall-carbon nanotubes have a variety of advantageous properties including good electrical conductivity and mechanical strength, and thus have been widely investigated for use in lithium-ion battery electrodes as conductive and microstructural additives, though they also possess some electrochemical activity. Their application to sodium-ion batteries has been less extensively researched, and therefore a greater understanding of the electrochemical reaction with sodium, and effects of slurry composition and electrolyte formulation is warranted, especially as these are likely components in future Na-ion electrode formulations. Here, we report the fabrication of aqueous and organic multi-wall carbon nanotube (MWCNT) negative electrodes processed by ball milling. The binder of choice is noted to greatly affect the electrochemical performance, both in terms of capacity retention and rate capability over a range of current densities from 25 to 500 mA g−1. Switching from a carbonate- to diglyme-based electrolyte considerably improves initial coulombic efficiencies (∼10%–60%), attributed to less extensive formation of solid electrolyte interphase, and enables a reversible mechanism with capacities up to 150 mAh g−1 over 100 cycles depending upon the binder used. Ex-situ characterization of the discharged and cycled carbon nanotubes by powder x-ray diffraction, transmission electron microscopy and Raman spectroscopy provide an insight into how MWCNTs undergo sodiation and demonstrate a partially reversible structural transformation during cycling when using the diglyme-based electrolyte. This work lays the foundation for a better understanding of these versatile materials, especially when used in the most promising alternative energy storage technology to lithium ion.

Lipid nanoparticle-based mRNA candidates elicit potent T cell responses.

The induction of a potent T cell response is essential for successful tumor immunotherapy and protection against many infectious diseases. In the past few years, mRNA vaccines have emerged as potent immune activators and inducers of a robust T cell immune response. The recent approval of the Moderna and the Pfizer/BioNTech vaccines based on lipid nanoparticles (LNP) encapsulating antigen-encoding mRNA has revolutionized the field of vaccines. The advantages of LNPs are their ease of design and formulation resulting in potent, effective, and safe vaccines. However, there is still plenty of room for improvement with respect to LNP efficacy, for instance, by optimizing the lipid composition and tuning LNP for specific purposes. mRNA delivery is known to be strongly dependent on the lipid composition of LNPs and the efficiency is mainly determined by the ionizable lipids. Besides that, cholesterol and helper lipids also play important roles in mRNA transfection potency. Here, a panel of LNP formulations was studied by keeping the ionizable lipids constant, replacing cholesterol with β-sitosterol, and changing the fusogenic helper lipid DOPE content. We studied the ability of this LNP library to induce antigen presentation and T cell proliferation to identify superior LNP candidates eliciting potent T cell immune responses. We hypothesize that using β-sitosterol and increasing DOPE content would boost the mRNA transfection on immune cells and result in enhanced immune responses. Transfection of immortal immune cell lines and bone marrow dendritic cells (BMDCs) with LNPs was studied. Delivery of mRNA coding for the model antigen ovalbumin (OVA-mRNA) to BMDCs with a number of LNP formulations, resulted in a high level of activation, as evidenced by the upregulation of the co-stimulatory receptors (CD40 and CD86) and IL-12 in BMDCs. The enhancement of BMDC activation and T cell proliferation induced by the introduction of β-sitosterol and fusogenic DOPE lipids were cell dependent. Four LNP formulations (C12-200-cho-10%DOPE, C12-200-sito-10%DOPE, cKK-E12-cho-10%DOPE and cKK-E12-sito-30%DOPE) were identified that induced robust T cell proliferation and enhanced IFN-γ, TNF-α, IL-2 expression. These results demonstrate that T cell proliferation is strongly dependent on LNP composition and promising LNP-mRNA vaccine formulations were identified.

Conveyance of sofosbuvir through vesicular lipid nanocarriers as an effective strategy for management of viral meningitis.

This study aimed to deliver a potential water-soluble antiviral drug (sofosbuvir) through optimized vesicular lipid nanocarriers (LNs) to the rat brain as a novel strategy against viral meningitis. A 23 factorial design approach was established to assess the effect of formulation composition and process variables on the physicochemical properties of the LNs. Sofosbuvir-loaded LNs (SLNs) were developed by lipid layer hydration method utilizing optimized parameters and evaluated for various in vitro characterizations like FTIR, DSC, XRD, FESEM, vesicle size, zeta potential, drug carrying capacity and drug release. Plasma and brain pharmacokinetic (PK) studies were conducted in Sprague-Dawley rats. FTIR data depicted the absence of any major interaction between the drug and the excipients. DSC revealed a sharp endothermic peak for the drug. XRD showed the amorphic nature of the SLNs. Optimized SLNs were spherical as depicted from FESEM with 42.43 nm size, -49.21 mV zeta potential, 8.31% drug loading and sustained drug release in vitro. Plasma/brain PK studies depicted significant improvement in key PK parameters, viz. AUC, AUMC, MRT, and Vd, compared to those for the free drug. A more than 3.5-fold increase in MRT was observed for optimized SLNs (11.2 h) in brain tissue compared to the free drug (3.7 h). Ex vivo hemolysis data confirmed the non-toxic nature of the SLNs to human red blood cells. In silico docking study further confirmed strong interaction between the drug and selected protein 4YXP (herpes simplex) with docking score of -7.5 and 7EWQ protein (mumps virus) with docking score of -7.3. The optimized SLNs may be taken for further in vivo studies to pave the way towards clinical translation.