Dual Carriers Research Articles

Mo‐Doped Perovskite Cathode Enables High‐Performance Cycling‐Stable Zinc‐Ion Batteries

AbstractManganese compounds have emerged as promising cathode materials for aqueous zinc‐ion batteries (AZIBs). But their broader applications are impeded by such cathodes' poor structure stability and sluggish ion transportation. Herein, these limitations are addressed by proposing high‐valence Mo doping regnant LaMnO3 perovskite oxide cathodes to develop high‐performance rate stable AZIBs. The optimized doped cathode contributes a highest specific capacity of 445 mAh g−1 at the current density of 0.5 A g−1, which maintains 206 mAh g−1 at 2 A g−1 and accompanies with a remarkable capacity retention of 114% beyond 1000 cycles for continuous charge/discharge process. The doping of multivalent Mo is revealed to boost the energy storage capacity and stabilize the electrode structure via various ex situ characterization and theoretical calculations. Importantly, the incorporation of Mo facilitates the acceleration of reaction kinetics and sufficient charge transfer with H+ and Zn2+ as dual charge carriers, where H+ plays a dominant role. This work provides a new perspective on developing innovative perovskite oxide cathodes with high‐valence metal doping for AZIBs.

Enhanced performance of red mud oxygen carrier for chemical looping combustion via tandem reactions

Biomethane power generation, particularly chemical looping combustion technology, has garnered significant attention recently due to its ability to capture CO2 in situ. In this study, dual bed layers oxygen carriers (DBL) for chemical looping combustion of methane were designed. The LaFe0.93Ni0.07O3 oxygen carrier with excellent CH4 partial oxidation was applied in upper bed layer and low-cost red mud was located into lower bed layer. This tandem reaction showed much higher methane conversion (87.1 %) than that over the single oxygen carrier of red mud (33.9 %) and the mechanically mixed oxygen carrier of LaFe0.93Ni0.07O3 and red mud (77.7 %). In addition, the mechanically mixed sample showed a quick deactivation, with the methane conversion dropping 54.2 % after 40 redox cycles due to the encapsulation of the active LaFe0.93Ni0.07O3 by red mud, while the double bed system showed high stability in the long-term redox cycle. The limitedly increased crystallite size of LaFeO3, as well as completely replenished lattice oxygen, were responsible for superior activity and stability of DBL. This study provides a new strategy to improve the efficiency of chemical looping combustion of methane in fixed bed reactor by tandem reactions over different oxygen carriers with complementary functions in terms of activity and cost.

Dual Polyanion Mechanism for Superionic Transport in BH4‐Based Argyrodites

AbstractPolyanion rotations are often linked to cation diffusion, but the study of multiple polyanion systems is scarce due to the complexities in experimentally determining their dynamic interactions. This work focuses on BH4‐based argyrodites, synthesized to achieve a high conductivity of 11 mS cm−1. Advanced tools, including high‐resolution X‐ray diffraction, neutron pair distribution function analysis, and mutinuclear magic‐angle‐spinning nuclear magnetic resonance (NMR) spectroscopy and relaxometry, along with theoretical calculations, are employed to unravel the dynamic intricacies among the dual polyanion lattice and active charge carriers. The findings reveal that the anion sublattice of Li5.07PS4.07(BH4)1.93 affords an even temporal distribution of Li among PS43− and BH4−, suggesting minimal trapping of the charge carriers. Moreover, the NMR relaxometry unveils rapid BH4− rotation on the order of ∼GHz, affecting the slower rotation of neighboring PS43− at ∼100 MHz. The PS43− rotation synchronizes with Li+ motion and drives superionic transport. Thus, the PS43− and BH4− polyanions act as two‐staged dual motors, facilitating rapid Li+ diffusion.

Productive use of energy of women-owned micro-, small-, and medium-sized enterprises: Insights from food and textile businesses in selected African countries

This paper presents a descriptive study focusing on the productive energy use of women-owned micro-, small-, and medium-sized enterprises that operate in Africa's food and textile sectors. Through a multidisciplinary approach, combining primary and secondary data collection methods, and integrating quantitative and qualitative tools, this study examines the relationship between the gender-based ownership structure of enterprises (i.e., sole female, female-female, and female-male) and energy consumption patterns, including demand levels, carrier use, access type (on-grid or off-grid), and expenditure. Despite limitations in scope and sample size, the findings shed light on gender-specific productive use practices.Findings show that female-owned businesses primarily rely on single or dual energy carriers, contrasting with female-male enterprises, which typically employ two or more energy carriers. Fuel usage varies among ownership structures, with diesel, biomass, and liquified petroleum gas being notable choices. Increasing diversity in ownership correlates with heightened awareness of energy metrics and monthly demand for electric and mechanical power, with some of the latter correlation also observed for thermal energy. Moreover, as ownership diversity increases, energy expenditure per kilogramme of production output decreases. Some sole female-owned enterprises surpass 100 USD/kg/month, female-female partnerships may reach 100 USD/kg/month, whereas female-male co-owned enterprises remain below 10 USD/kg/month.Beyond contributing to understanding gendered productive energy practices, this research also emphasises the importance of gender mainstreaming in productive use and energy access interventions. It highlights the need for renewable energy solutions, capacity-building programmes, and further research to address efficiency and accessibility challenges faced by women entrepreneurs.

Single composite electrolyte prepared by infiltration and characterization

Oxygen-ion and proton-conducting electrolytes should be combined into a composite to improve fuel cell capacity and electrocatalytic efficiency. To realize a single membrane of a composite electrolyte with dual charge carriers, we use only a single process. A BaZr0.8Ni0.01Y0.19O3 (BZNY) proton-conducting electrolyte solution and suspension are infiltrated into a porous oxygen-ion-conducting electrolyte (La0.75Sr0.2Ba0.05)0.175Ce0.825O1.891 (LSBC) substrate using a simple pumping process. The infiltration of BZNY into the porous LSBC results in a gradient composition of BZNY. The obtained single-composite electrolyte, BZNY-LSBC, possesses individual perovskite and fluorite crystal structures after sintering. The BZNY solution infiltrates the porous LSBC substrate to a smaller depth than the phase-preformed nano-BZNY slurry. The effective infiltration depth is approximately 50 μm for the BZNY solution, and 300 μm for the nano-BZNY into a 400 μm thickness of LSBC. The infiltrated composite electrolyte exhibites lower conductivity compared to the solid-state-prepared single-phase LSBC electrolyte at 600 °C, but almost the same conductivity at 800 °C from the AC impedance analyses. When the Sr2Fe1.5Mo0.5O6 (SFM) are applied as symmetric electrodes, the SFM|BZNY-LSBC|SFM fuel cells maintain the higher open circuit voltage of 0.8 V than 0.5 V for SFM|LSBC|SFM fuel cells at 600 °C. The fuel cell with nano-BZNY infiltrated composite electrolyte achieves over double power density than cells with single LSBC and solution BZNY infiltration electrolytes at 600 °C that may be due to the proton conduction enhancement at lower temperature and further promotes the triple power density at 800 °C contributed from the oxygen ions conduction of LSBC and BZNY at high temperature. Those results provide evidence that dual ions pass through individual conduction paths in a two-phase composite electrolyte.

Inhalable porous particles as dual micro-nano carriers demonstrating efficient lung drug delivery for treatment of tuberculosis

Inhalation therapy treating severe infectious disease is among the more complex and emerging topics in controlled drug release. Micron-sized carriers are needed to deposit drugs into the lower airways, while nano-sized carriers are of preference for cell targeting. Here, we present a novel and versatile strategy using micron-sized spherical particles with an excellent aerodynamic profile that dissolve in the lung fluid to ultimately generate nanoparticles enabling to enhance both extra- and intra-cellular drug delivery (i.e., dual micro-nano inhalation strategy). The spherical particles are synthesised through the condensation of nano-sized amorphous silicon dioxide resulting in high surface area, disordered mesoporous silica particles (MSPs) with monodispersed size of 2.43 μm. Clofazimine (CLZ), a drug shown to be effective against multidrug-resistant tuberculosis, was encapsulated in the MSPs obtaining a dry powder formulation with high respirable fraction (F.P.F. <5 μm of 50%) without the need of additional excipients. DSC, XRPD, and Nitrogen adsorption-desorption indicate that the drug was fully amorphous when confined in the nano-sized pores (9–10 nm) of the MSPs (shelf-life of 20 months at 4 °C). Once deposited in the lung, the CLZ-MSPs exhibited a dual action. Firstly, the nanoconfinement within the MSPs enabled a drastic dissolution enhancement of CLZ in simulated lung fluid (i.e., 16-fold higher than the free drug), increasing mycobacterial killing than CLZ alone (p = 0.0262) and reaching concentrations above the minimum bactericidal concentration (MBC) against biofilms of M. tuberculosis (i.e., targeting extracellular bacteria). The released CLZ permeated but was highly retained in a Calu-3 respiratory epithelium model, suggesting a high local drug concentration within the lung tissue minimizing risk for systemic side effects. Secondly, the micron-sized drug carriers spontaneously dissolve in simulated lung fluid into nano-sized drug carriers (shown by Nano-FTIR), delivering high CLZ cargo inside macrophages and drastically decreasing the mycobacterial burden inside macrophages (i.e., targeting intracellular bacteria). Safety studies showed neither measurable toxicity on macrophages nor Calu-3 cells, nor impaired epithelial integrity. The dissolved MSPs also did not show haemolytic effect on human erythrocytes. In a nutshell, this study presents a low-cost, stable and non-invasive dried powder formulation based on a dual micro-nano carrier to efficiently deliver drug to the lungs overcoming technological and practical challenges for global healthcare.

Male with an apparently normal phenotype carrying a BRCA1 exon 20 duplication in trans to a BRCA1 frameshift variant

BackgroundReports of dual carriers of pathogenic BRCA1 variants in trans are extremely rare, and so far, most individuals have been associated with a Fanconi Anemia-like phenotype.MethodsWe identified two families with a BRCA1 in-frame exon 20 duplication (Ex20dup). In one male individual, the variant was in trans with the BRCA1 frameshift variant c.2475delC p.(Asp825Glufs*21). We performed splicing analysis and used a transcription activation domain (TAD) assay to assess the functional impact of Ex20dup. We collected pedigrees and mapped the breakpoints of the duplication by long- and short-read genome sequencing. In addition, we performed a mitomycin C (MMC) assay from the dual carrier using cultured lymphoblastoid cells.ResultsGenome sequencing and RNA analysis revealed the BRCA1 exon 20 duplication to be in tandem. The duplication was expressed without skipping any one of the two exon 20 copies, resulting in a lack of wild-type transcripts from this allele. TAD assay indicated that the Ex20dup variant has a functional level similar to the well-known moderate penetrant pathogenic BRCA1 variant c.5096G > A p.(Arg1699Gln). MMC assay of the dual carrier indicated a slightly impaired chromosomal repair ability.ConclusionsThis is the first reported case where two BRCA1 variants with demonstrated functional impact are identified in trans in a male patient with an apparently normal clinical phenotype and no BRCA1-associated cancer. The results pinpoint a minimum necessary BRCA1 protein activity to avoid a Fanconi Anemia-like phenotype in compound heterozygous status and yet still predispose carriers to hormone-related cancers. These findings urge caution when counseling families regarding potential Fanconi Anemia risk. Furthermore, prudence should be taken when classifying individual variants as benign based on co-occurrence in trans with well-established pathogenic variants.

Melanin-inspired conductive thin films for multimodal-sensing wearable on-skin electronics

Electronic skins (e-skins), composed of various flexible sensors, mimic the sensing functions of human skin aiming for both healthcare monitoring and prosthetics development applications. So far different multi-component e-skin devices aimed to fulfill different requirements (biocompatibility, skin adhesion, flexibility, conductivity, sensitivity towards biological stimuli and stretchability) have been reported. However, the obtaining of such devices combining all the above requirements within a single material that simplifies not only cost but specially functioning still remains a challenge. For this, catechol-based materials have attracted special attention due to their adhesive properties, compatibility and melanin-like electrical conduction. In this work, 2,3,6,7,10,11 – hexahydroxy triphenylene (HHTP) was used as catechol moiety in a typical melanin-like polymerization, resulting in a free-standing melanin-inspired film (MN-film). The obtained MN-film showcased good conductivities with dual charge carriers (electrons and ions) under different environments, i.e. pure water and buffers simulating sweat. Large biocompatibility, adhesion and conformability to skin were obtained as well, allowing to implement the film in wearable electronic on-skin devices on porcine skin. Measurements in wearable devices indicated large sensitivity towards different stimuli (strain, motion and temperature) under sweat-like conditions.

Zein - laponite coacervate aided co-delivery of curcumin and cisplatin towards MDA-MB-231 breast cancer cells: Validating the concept

Cancer cell resistance towards drugs leads to limited drug efficacy and therefore, combination therapy of drugs has emerged as a solution. In addition to this, the importance of a carrier system for the co-delivery of drugs to improve the potential of anti-cancer drug efficacy cannot be overlooked. Nowadays, polymer-rich dense phases of liquid droplets, known as coacervates, have emerged as an appealing option to be utilised as drug carriers. Our previous study which reported the complexation between zein and laponite to form coacervates and their future prospect as dual drug carriers has been extended in this work. The present work has validated the usefulness of the synthesized coacervate as a dual-drug carrier for a hydrophilic drug (cisplatin) and a hydrophobic drug (curcumin) towards a breast cancer cell line (MDA-MB-231). The MTT assay and flow cytometry data for MDA-MB-231 cells suggested that the coacervate carrying dual drugs effectively transported anticancer drugs to the cancer cells, thereby arresting their cell cycle in the S phase (by neutral coacervates, X1) and in the G2/M phase (by charged coacervates, X2). Further, it is also revealed that the amount of cisplatin needed to achieve half maximal inhibitory concentration (IC50) was reduced by a maximum of 70% when flavonoid (curcumin) was used in combination with cisplatin due to synergistic effect.

Double carbon modified Na3V2(PO4)3 with dual charge carriers and high performance synthesized in-situ in polypyrrole and chitosan quaternary ammonium hydrogel

Sodium-ion batteries (SIBs) are regarded as the most promising battery to replace lithium-ion batteries (LIBs) in the future. Na3V2(PO4)3 (NVP), as an ideal positive electrode material for SIBs, is limited by poor electronic conductivity and low reversible capacity. In this paper, the double carbon resources of chitosan quaternary ammonium hydrogel (CHACC) and Polypyrrole (PPy) were introduced into NVP. Through the construction of double charge carriers, the high conductivity and the high reversible capacity of NVP which broke the theoretical limit were achieved. The introduction of CHACC brings the second charge carrier, ClO4−, in addition to Na+ in NVP system. Furthermore, the conductive network and defect-rich carbon coatings formed by CHACC and PPy significantly improve the electronic conductivity and kinetics of the electrode. Comprehensively, the detailed functional mechanism of dual carriers in NVP is deeply investigated by ex-situ FTIR and XPS, revealing that ClO4− utilizes the N+ in the carbonized substrate of CHACC and PPy as the binding sites to reversibly inserted/extracted from the carbon layer to provide additional capacities. Notably, the optimized CHACC-PPy-NVP submits superior sodium storage performance. It delivers a capacity of 148.3 and 139.3 mAh g−1 at 0.1 and 1C, significantly exceeding the theoretical capacity (117.6 mAh g−1). Even at 140C, it still maintains a capacity value of 88.9 mAh g−1 with 75.7 mAh g−1 remaining after 2000 cycles, corresponding to a low decay rate of 0.007 % per cycle.

Double Trouble: Association of Malignant Melanoma with Sporadic and Genetic Forms of Parkinson's Disease and Asymptomatic Carriers of Related Genes: A Brief Report.

Introduction: Previous epidemiological evidence has established the co-occurrence of malignant melanoma (MM) and Parkinson's disease (PD). Shared molecular mechanisms have been proposed to be implicated in this relationship. The aim of the present study was to assess the prevalence of MM in patients with sporadic and genetic types of PD, as well as in asymptomatic carriers of PD-related genes. Methods: Data regarding past medical history and concomitant disease of 1416 patients with PD (including 20 participants with prodromal disease who phenoconverted to PD), 275 healthy controls (HCs) and 670 asymptomatic carriers of PD-related genes were obtained from the database of the Parkinson's Progression Markers Initiative (PPMI). Focus was placed on information about a medical record of MM. We also retrieved data regarding the genetic status of selected PPMI participants with a positive MM history. Results: In total, 46 patients with PD reported a positive MM history. Concerning the genetic forms of PD, nine of these PD patients (2.47%) carried a Leucine Rich Repeat Kinase 2 (LRRK2) gene mutation (mainly the G2019S), while eight (4.49%) harbored a Glucocerebrosidase (GBA) gene mutation (mainly the N370S). No alpha-synuclein (SNCA) gene mutation was identified in patients with an MM history. The remaining 29 PD patients (3.5%) were genetically undetermined. In total, 18 asymptomatic carriers of PD-related genes had a positive medical history for MM: among them, 10 carried an LRRK2 gene mutation (2.69%) and 10 a GBA gene mutation (3.51%) (2 were dual carriers). MM history was identified for seven HCs (2.5%). Conclusions: We replicated the previously reported association between genetically undetermined PD (GU-PD) and MM. A correlation of LRRK2 mutations with the development of MM could not be verified in either symptomatic PD patients or asymptomatic carriers, implicating distinct pathogenetic mechanisms as compared to GU-PD. Importantly, despite the limited literature evidence on Gaucher disease, this study highlights for the first time the relatively high prevalence of MM among asymptomatic and symptomatic PD GBA mutation carriers, with potential clinical implications.

CuS Nanoparticles Modified ZnO/CdS Dual Direct Z-type Heterostructure Nanocomposite for Efficient Visible-Light Photocatalytic Degradation RhB

The low-temperature hydrothermal and water bath methods are used to manufacture CuS@ZnO/CdS catalyst. The Rhodamine B degradation rate constant of CuS@ZnO/CdS is around 1.53 × 10−2 min−1, which is 3.9 times greater than that of ZnO. The coupling of CdS and loading of CuS onto ZnO surfaces were evaluated using XRD, SEM, TEM, and XPS. SEM demonstrated that 5 mg of CdS was the most effective in controlling the shape of ZnO nanoflakes. Ultraviolet-visible absorption (UV–vis) and Photoluminescence (PL) spectra reveal that CdS and CuS decreased the bandgap of ZnO and boosted its ability to absorb visible light. Transient photocurrent response (TPR) and electrochemical impedance spectra (EIS) display that CdS and CuS facilitate the quick separation of photoexcited carriers in ZnO. Notably, the optimal weight ratio of CuS was determined to be 15%, since excessive amounts of CuS would operate as recombination centers and cover active sites. Additionally, the dual Z-scheme carriers movement mechanism was proposed using sacrificed agent experiments, and TOC analyzed the mineralization rate of RhB after degradation. In this study, CuS@ZnO/CdS photocatalyst degraded RhB nearly 99% in 80 min, which is superior to the earlier photocatalysts. Therefore, this article holds great significance in the practical application of metal chalcogenide-modified ZnO-based photocatalysts with superior visible light-induced degradation performance in environmental purification.

Constructing 3D cross-connected networks in spongy MgO/Ni/MWCNT composites to synchronously boost microwave absorption and thermal conductivity

To address the issues of electromagnetic (EM) radiation and waste heat engendered in modern electrics, we pioneer the utilization of 3D cross-connected MgO/Ni/MWCNT networks as a magnetic-dielectric-dual-loss filler with electron-phonon dual thermal carriers to synchronously boost EMW absorption and thermal conductivity. The carbothermic reduction of magnesium oxalate/nickel oxalate core-shell hexahedra produced from a cryogenic precipitation/precipitate transfer route causes the in-situ self-catalytic growth of MWCNTs on the surfaces of porous MgO/Ni composites. The component, microstructure, and texture of the composites and their resulting performance can be tuned by some dynamic factors (i.e., [Ni2+], Ts, etc.). The spongy MgO/Ni/MWCNT composites formed under [Ni2+] = 1.6 M and Ts = 600 ℃ exhibit the optimal EMW absorption and thermal conductivity. Compared with the most previously reported materials, they have a larger thermal conductivity (3.61 W/(m⋅K)), a larger EAB/d value (∼4.61 GHz/mm), stronger absorption (−51.33 dB), and a smaller thickness (1.7 mm). The synchronously enhanced properties are attributed to magnetic/dielectric dual losses, electron/phonons dual thermal carriers, and 3D interconnected networks in MgO/Ni/MWCNT composites, which generate the strong attenuation, good low-frequency matching performance, and continuous heat transfer path. Noteworthy, spongy MgO/Ni/MWCNT composites are promising as a multifunctional filler to address the issues of EMI and thermal dissipation.

Clarithromycin-Loaded Submicron-Sized Carriers: Pharmacokinetics and Pharmacodynamic Evaluation.

The current study aims to improve clarithromycin bioavailability and effectiveness in complicated intra-abdominal infection management. Therefore, clarithromycin-loaded submicron dual lipid carriers (CLA-DLCs) were developed via hot high shear homogenization technique and evaluated for colloidal parameters, release behavior, stability study, and in-vitro antibiofilm activity. Bioavailability and therapeutic efficacy of optimized formulation on hampering cytokines storm induction was determined in E. coli-induced peritonitis. The developed CLA-DLCs (particle size 326.19 ± 24.14 nm, zeta potential -31.34 ± 2.81 mV, and entrapment efficiency 85.78 ± 4.01%) exhibited smooth spherical shapes and sustained in vitro release profiles. Long-term stability study of optimized CLA-DLCs ensured maintenance of colloidal parameters for 1 year at room temperature. In vitro antimicrobial studies revealed 3.43-fold higher anti-biofilm activity of CLA-DLCs compared with clarithromycin. In addition, the relative bioavailability of CLA-DLCs was enhanced 5.89-fold compared to pure drug in rats. The remarkable decrease in microbial burden in blood as well as tissues, along with oxidative stress markers (lipid peroxidation, myeloperoxidase activity, and carbonylated protein level) and immunological markers (total leukocyte count, neutrophil migration, NO, TNF-, and IL-6) on treatment with CLA-DLCs enhanced the survival in a rat model of peritonitis compared with the pure drug and untreated groups. In conclusion, CLA-DLCs hold promising potential in management of intra-abdominal infections and prevention of associated complications.

IR780-doped cobalt ferrite nanoparticles@poly(ethylene glycol) microgels as dual-enzyme immobilized micro-systems: Preparations, photothermal-responsive dual-enzyme release, and highly efficient recycling

To solve the problems of separating dual enzymes from the carriers of dual-enzyme immobilized micro-systems and greatly increase the carriers’ recycling times, photothermal-responsive micro-systems of IR780-doped cobalt ferrite nanoparticles@poly(ethylene glycol) microgels (CFNPs-IR780@MGs) are prepared. A novel two-step recycling strategy is proposed based on the CFNPs-IR780@MGs. First, the dual enzymes and the carriers are separated from the reaction system as a whole via magnetic separation. Second, the dual enzymes and the carriers are separated through photothermal-responsive dual-enzyme release so that the carriers can be reused. Results show that CFNPs-IR780@MGs is 281.4 ± 9.6 nm with a shell of 58.2 nm, and the low critical solution temperature is 42 °C, and the photothermal conversion efficiency increases from 14.04% to 58.41% by doping 1.6% of IR780 into the CFNPs-IR780 clusters. The dual-enzyme immobilized micro-systems and the carriers are recycled 12 and 72 times, respectively, and the enzyme activity remains above 70%. The micro-systems can realize whole recycling of the dual enzymes and carriers and further recycling of the carriers, thus providing a simple and convenient recycling method for dual-enzyme immobilized micro-systems. The findings reveal the micro-systems’ important application potential in biological detection and industrial production.

Calcium peroxide-mediated bioactive hydrogels for enhanced angiogenic paracrine effect and osteoblast proliferation

Polymeric hydrogels have been extensively utilized as therapeutic vehicles for delivering cells or bioactive molecules to enhance bone tissue regeneration. Among these factors, growing evidence demonstrates that oxygen (O2) and calcium ions (Ca2+) play pivotal roles in bone repair and regeneration, including cell proliferation and vascularization. Herein, we report on gelatin-based bioactive matrices as dual carriers of O2 and Ca2+ for vascularized bone tissue regeneration. Bioactive hydrogels were prepared through a calcium peroxide (CaO2)-mediated crosslinking reaction. We demonstrated that the hydrogels have controllable mechanical properties depending on the composition (G′:300–1700 Pa). We also demonstrated that the hydrogels released Ca2+ in a sustained manner for two days (2.6–2.8 mM) and released O2 (DOmax: G7C0.5, 97.9% pO2; G7C0.25, 82.7% pO2; G7C0.125, 65.5% pO2), providing transient hyperoxic conditions to cells in vitro. Notably, we found that our bioactive hydrogels enhanced the proliferation of pre-osteoblasts (MC3T3-E1) and gene expression of vascular endothelial growth factor (VEGF) from mesenchymal stem cells (MSCs). In summary, our O2- and Ca2+-releasing hydrogels show potential as bioactive hydrogels for vascularized bone tissue regeneration.

Dual‐drug delivery of sodium ceftriaxone and metronidazole by applying salt‐assisted chitosan nanoparticles: Stability, drug release, and time‐kill assay study against Bacteroides fragilis

AbstractThe purpose of this study was to develop a polymeric biomaterial with regulated dual drug release and increased bactericidal strength of the antibiotics sodium ceftriaxone (CTX) and metronidazole (MTZ) for the treatment of intra‐abdominal infections. Chitosan nanoparticles (CS NPs) were produced by ionic crosslinking process in the presence of NaCl monovalence salt. The antibacterial activity and drug release behavior of CS NPs were investigated against anaerobic Bacteroides fragilis. The optimum initial drug ratio for designing dual drug carriers containing CTX and MTZ in a 4:3 ratio was 1:1. After 6 months, the salt‐assisted CTX‐MTZ‐loaded CS NPs were 300 nm in size and had a polydispersity index of 0.09 with high stability. It has been demonstrated that drug release from NPs is more tightly controlled than drug release from free drugs. Furthermore, the data show that the minimum inhibitory concentration and minimum bactericidal concentration for nanostructure carriers are one‐quarter of those of free medicines. Free drugs could completely kill the bacterium after 24 h, but the dual drug carrier could kill the bacteria in 10 h. Finally, salt‐assisted CTX‐MTZ‐loaded CS NPs were proposed as a feasible alternative to standard intra‐abdominal infection treatment.

Decreased Infliximab Concentrations in Patients With Inflammatory Bowel Disease Who Carry a Variable Number Tandem Repeat Polymorphism in the Neonatal Fc Receptor or Variant HLADQA1*05G>A Genotype.

Multiple variables contribute to variation in patient exposure and response to tumor necrosis factor alpha antagonist biologics such as infliximab. This study aimed to assess the association between maintenance-phase infliximab concentrations and genetic variation in HLADQA1*05G>A and fragment crystallisable (Fc) fragment of IgG receptor and transporter (FCGRT) among patients with inflammatory bowel disease. A cross-sectional study was carried out in participants with inflammatory bowel disease prescribed infliximab who were in the maintenance phase of treatment. Participants were genotyped for the presence of the FCGRT variable number tandem repeat (VNTR) and HLADQA1*05G>A (rs74291249). A point estimate of the infliximab trough concentration during the maintenance phase was determined using a standard enzyme-linked immunosorbent assay for each patient. Other variables associated with infliximab pharmacokinetics were collected. A total of 156 participants with inflammatory bowel disease were included from 2 tertiary care centers affiliated with Western University, London, Canada. Median infliximab trough concentrations were lower in participants who carried the FCGRT VNTR 2/3 or 2/2 (4.14 µg/mL; interquartile range [IQR], 6.48 µg/mL) vs wild type individuals (7.00 µg/mL; IQR, 7.66; P = .0027). Median infliximab trough concentrations were significantly lower in participants who were HLADQA1*05G>A variant carriers (4.73µg/mL; IQR, 4.79) vs wild type individuals (7.85µg/mL; IQR, 7.44; P = .0006). A significant decrease in infliximab trough concentrations was seen in individuals who were dual carriers of variant polymorphisms in HLADQA1*05G>A and FCGRT VNTR (no variants, 8.96µg/mL; IQR, 6.84 vs one variant, 4.96 µg/mL; IQR, 4.95 vs dual variants, 0.86µg/mL; IQR, 5.82). FCGRT VNTR and HLADQA1*05G>A are associated with lower maintenance-phase infliximab concentrations, particularly among patients who carry both variants.

Nanostructured Lipid Carrier-Based Codelivery of Raloxifene and Naringin: Formulation, Optimization, In Vitro, Ex Vivo, In Vivo Assessment, and Acute Toxicity Studies.

This work aimed to develop dual drug-loaded nanostructured lipid carriers of raloxifene and naringin (RLX/NRG NLCs) for breast cancer. RLX/NRG NLCs were prepared using Compritol 888 ATO and oleic acid using a hot homogenization–sonication method and optimized using central composite design (CCD). The optimized RLX/NRG NLCs were characterized and evaluated using multiple technological means. The optimized RLX/NRG NLCs exhibited a particle size of 137.12 nm, polydispersity index (PDI) of 0.266, zeta potential (ZP) of 25.9 mV, and entrapment efficiency (EE) of 91.05% (raloxifene) and 85.07% (naringin), respectively. In vitro release (81 ± 2.2% from RLX/NRG NLCs and 31 ± 1.9% from the RLX/NRG suspension for RLX and 93 ± 1.5% from RLX/NRG NLCs and 38 ± 2.01% from the RLX/NRG suspension for NRG within 24 h). Concurrently, an ex vivo permeation study exhibited nearly 2.3 and 2.1-fold improvement in the permeability profiles of RLX and NRG from RLX/NRG NLCs vis-à-vis the RLX/NRG suspension. The depth of permeation was proved with CLSM images which revealed significant permeation of the drug from the RLX/NRG NLCs formulation, 3.5-fold across the intestine, as compared with the RLX/NRG suspension. An in vitro DPPH antioxidant study displayed a better antioxidant potential of RLX/NRG in comparison to RLX and NRG alone due to the synergistic antioxidant effect of RLX and NRG. An acute toxicity study in Wistar rats showed the safety profile of the prepared nanoformulations and their excipients. Our findings shed new light on how poorly soluble and poorly permeable medicines can be codelivered using NLCs in an oral nanoformulation to improve their medicinal performance.

Combinatorial delivery of Ribociclib and green tea extract mediated nanostructured lipid carrier for oral delivery for the treatment of breast cancer synchronising in silico, in vitro, and in vivo studies

Purpose The current research investigated the development and evaluation of dual drug-loaded nanostructure lipidic carriers (NLCs) of green tea extract and Ribociclib. Method In silico study were performed to determine the effectiveness of combinational approach. The prepared NLCs were subjected to in vitro drug release, lipolysis, haemolysis and cell line studies to assess their in vivo prospect. Results In silico study was done to get docking score of EGCG (−8.98) close to Ribociclib (−10.78) in CDK-4 receptors. The prepared NLCs exhibited particle size (175.80 ± 3.51 nm); PDI (0.571 ± 0.012); and %EE [RBO (80.91 ± 1.66%) and GTE 75.98 ± 2.35%)] respectively. MCF-7 cell lines were used to evaluate the MTT assay, cellular uptake and antioxidant (ROS and SOD) of prepared NLCs. In vitro drug release showed the controlled release up to 72 h. In vitro lipolysis and in vitro haemolysis studies showed the availability of drugs at absorption sites and the greater in vivo prospects of NLCs respectively. Pharmacokinetic study revealed a 3.63-fold and 1.53-fold increment in RBO and GTE bioavailability in female Wistar rats respectively. Conclusion The prominent potential of green tea extract and RBO-loaded NLCs in enhancing their therapeutic efficacy for better treatment of breast cancer.