α-Lactalbumin based scaffolds for infected wound healing and tissue regeneration.

Interruption of wound healing by multi-drug resistant-bacterial infection is a harmful issue for the worldwide health care system, and conventional treatment approaches may not resolve this issue due to antimicrobial resistance. So, there is an unmet need to develop scaffolds with intrinsic wound healing properties to combat bacterial-infected wounds. Inspired by the α-lactalbumin's (Lalb's) ability to promote collagen synthesis, we herein electrospun Lalb with cephalexin (CPL) and epigallocatechin (EP) to produce nanofibers (CE-Lalb NFs) to solve this issue. The CE-Lalb NFs were prepared using the electrospinning technique and subjected to physicochemical characterizations, in vitro, and in vivo assessments. The CE-Lalb NFs promoted fibroblast migration, proliferation, and collagen synthesis, while CPL/EP annihilated MRSA and E. coli infections. Physicochemical characterizations proved the successful fabrication and doping of CE-Lalb NFs. Antimicrobial assays and fractional inhibitory concentration index (FICI) declared synergistic antibacterial activity of CE-Lalb NFs against MRSA and E. coli. The in vivo and immunohistochemical data evidenced its exceptional potential for wound healing, promoting growth factor, collagen synthesis, and reduced scar formation. The presence of mature collagen, fewer inflammatory cytokines, increased expression of blood vessels, and low expression of IL-6 at the wound site support in vitro and in vivo results. In our view, the tailored scaffold is the next step for personalized wound dressings that could meet patients with infected wounds' unmet needs by the subscription of noninvasive and easily navigable therapeutic options.

Obstructed vein delivery of ceftriaxone via poly(vinyl-pyrrolidone)-iodine-chitosan nanofibers for the management of diabetic foot infections and burn wounds.

Superficial skin injuries especially burn injuries and unhealed diabetic foot open wounds remain troubling for public health. The healing process is often interrupted by the invasion of resistant pathogens that results in the failure of conventional procedures outside the clinical settings. Herein, we designed nanofibers dressing with intrinsic antibacterial potential of poly(vinyl-pyrrolidone)-iodine/ poly (vinyl)-alcohol by electrospinning with chitosan encapsulating ceftriaxone (CPC/NFs). The optimized electrospun CPC/NFs exhibited smooth surface morphology with average diameter of 165 ± 7.1 nm, drug entrapment and loading efficiencies of 76.97 ± 4.7 % and 8.32 ± 1.73 %, respectively. The results displayed smooth and uniformed fibers with adequate thermal stability and ensured chemical doping. The enhanced in vitro antibacterial efficacy of CPC/NFs against resistant E. coli isolates and biosafety studies encourage the use of designed nanofibers dressing for burn injuries and diabetic foot injuries. In vivo studies proved the healing power of dressing for burn wounds model and diabetic infected wounds model. Immunofluorescence investigation of the wound tissue also suggested promising healing ability of CPC/NFs. The designed approach would be helpful to treat these infected skin open wounds in the hospitals and outside the clinical settings.

A standardized chamuangone enriched extract from Garcinia cowa Roxb. leaves shows acute and sub-acute safety.

ETHNOPHARMACOLOGICAL RELEVANCE: The safety assessment of herbal products is critical for their appropriate pharmacological applications. Garcinia cowa Roxb., commonly known as Cha-muang in Thai, has ethnopharmacological relevance for inflammation, infectious diseases, and diabetes. The leaf extracts of G. cowa have been extensively reported for their anticancer, anti-inflammatory, antimicrobial, and antioxidant effects. Notably, chamuangone is their major active constituent that contributes to various pharmacological properties. AIM OF THE STUDY: The current study aims to establish a standardized chamuangone enriched extract (CEE) and assess its acute and sub-acute toxicities in animal models. METHODOLOGY: CEE was established from G. cowa leaves using a microwave-assisted extraction (MAE), followed by fractionation and enrichment through silica gel vacuum and column chromatography. The concentration of chamuangone in the extract was quantified using a validated quantitative high-performance liquid chromatography (HPLC) method. The safety profiles of CEE were thoroughly evaluated in rodents according to the Organization for Economic Cooperation and Development (OECD) 425 and 407 guidelines. The effects on oxidative stress markers such as superoxide dismutase (SOD), reduced glutathione (GSH), catalase (CAT), and malondialdehyde (MDA) levels were also evaluated in various organs. RESULTS: Based on the quantitative HPLC analysis, the CEE contained 73.0 ± 2.0% w/w of chamuangone. In the acute toxicity study, following up and down procedure the female rats were dosed with CEE at 1750 and 550 mg/kg body weight (b.w.), with CEE 1750 mg/kg b.w. was toxic, causing mortality, while CEE 550 mg/kg b.w. was deemed safe. An LD50 value was calculated according to the standard protocols, resulting in 970 mg/kg b.w. In histopathological examination, 550 mg/kg b.w. of CEE was safe in all the selected organs, while the 1750 mg/kg b.w. CEE treated rats exhibited toxic effects in histological tissues sections in the form of necrosis in the brain, cardiac muscle hypertrophy, liver inflammation, mild untoward effect in the spleen, fibrosis in the lungs, pancreatitis, pyelonephritis, and ovarian cyst. Administration of CEE at doses of 550 mg/kg b.w. (single dose) in the acute and 100 mg/kg b.w. (regularly 28-days) in the sub-acute toxicity studies significantly (p < 0.05) decreased levels of uric acid, triglycerides, and cholesterol. Importantly, the CEE (550 and 100 mg/kg b.w.) also significantly increased the levels of antioxidant enzymes (SOD, GSH, and CAT) and decreased MDA levels. Normal histopathology was observed in the sub-acute toxicity study in all treated groups. CONCLUSION: This study successfully concludes that CEE at a dose of 100 mg/kg b.w. is safe for therapeutic application or use as a chemopreventive functional food utilizing green extraction methods. However, chronic toxicity studies are further recommended to validate safety concerns over an extended period.

Stimuli-sensitive biomimetic nanoparticles for the inhibition of breast cancer recurrence and pulmonary metastasis.

Biomimetic nanoparticles represent a promising avenue for mitigating rapid clearance by the reticuloendothelial system (RES); however, current challenges include insufficient tumour targeting, suboptimal adhesion, and inadequate localized drug release within tumour regions. These shortcomings contribute to persistent contests, such as recurrence and pulmonary metastasis, even with advanced breast cancer therapies. Stimuli-sensitive drug release can furbish the membrane coated nanoparticles for their efficiency against the stated problems. To enhance the efficacy of biomimetic nanoparticles in addressing these issues, we proposed a versatile, stimuli-responsive drug delivery system by encapsulating doxorubicin (Dox) and perfluorohexane (PFH) within poly (lactic-co-glycolic acid) (PLGA) nanoparticles, subsequently coated with macrophage-derived cell membranes. Within this framework, PFH serves as the mediator for ultrasonic (US)-irradiation-triggered drug release specifically within tumour microenvironment, while the macrophage-derived cell membrane coating enhances cell adhesion, enables immune evasion, and natural tumour-homing ability. The characterization assays and in vitro evaluations yielded encouraging results, indicating enhanced targeting and release efficiencies. In vivo studies demonstrated marked inhibitory effects on both breast cancer recurrence and pulmonary metastasis. The resulting data indicate that these engineered nanoparticles have notable potential for targeted delivery and controlled release upon US irradiation, thereby offering significant therapeutic efficacy against primary breast cancer, pulmonary metastasis, and recurrent malignancies. Our findings lay the groundwork for a novel clinical approach, representing an intriguing direction for ongoing investigation by oncologists.

Bio-evaluations of sericin coated hesperidin nanoparticles for gastric ulcer management.

Gastric ulcers are worrying, and their worsening conditions may result in bleeding in the internal lining of the stomach. The problem is annoying, and both patients and professionals are still not satisfied with the available treatment options. Hesperidin, a flavonoid molecule with potent anti-inflammatory and antioxidant effects, can work like witchcraft to repair gastric ulcers and preserve the stomach lining. Here, we employed a strategy that involved covering the surface of the nano-lipid carriers (NLCs) with sericin before encasing the hesperidin within (Se-He-NLC). Sericin, a biodegradable polymer increases the muco-adhesion with stomach lining and deployment of hesperidin in controlled manner. Se-He-NLCs were physico-chemically characterized for drug loading, encapsulation, particle size, morphology, drug release, chemical stability, and chemical bonding. The nanocarriers showed first order drug release in a controlled manner. Se-He-NLCs showed better in vitro permeation and ex vivo mucoadhesion, thereby by promoting the in vivo bioavailability. Se-He-NLCs also promoted the reduced glutathione (GSH) and glutathione-S-transferase (GST) levels by 2.24- and 1.61-folds, respectively in the stomach lining, and also the regulation of superoxide dismutase (SOD) and catalase (CAT) activities parallel to the control group. In addition, tissues lipid hydroperoxides (LOOH) and myeloperoxidase (MPO) activity were reduced significantly with Se-He-NLCs administration. Se-He-NLC therapy of stomach ulcers in vivo demonstrated better binding ratio and ulcer healing potential. This approach reveals huge capacity for delivering therapies to treat gastric ulcers based on the clinical significance of sericin coated hesperidin nanocarriers in gastric ulcer treatment.

Self-emulsifying micelles as a drug nanocarrier system for itraconazole oral bioavailability enhancement; in vitro and in vivo assessment.

Itraconazole (ITZ) is a renowned antifungal medication, however its therapeutic efficacy is limited by low solubility and oral bioavailability. The current research work attempted to augment the oral bioavailability of ITZ by incorporating into self-emulsifying micelles (SEMCs). To fabricate the SEMCs, various preparation techniques including physical mixture, melt-emulsification, solvent evaporation and kneading, were opted by using different weight ratio of drug and solubilizers i.e. Gelucire-50/13 or Gelucire-44/14 and characterized both in vitro and in vivo. The prepared SEMCs were found to be in the size range from 63.4 ± 5.2 to 284.2 ± 19.5 nm with surface charges ranging from -16 ± 1.2 to -27 ± 2.0 mV. The drug solubility was improved to a reasonable extent with all investigated formulations, however, SEMCs in group 6 prepared by kneading method (KMG6) using Gelucire-44/14: drug (10:1 presented 87.6 folds' increase (964.93 ± 2 µg/mL) compared to solubility of crystalline ITZ (11 ± 2 µg/mL) through kneading method. In addition, KMG6 SEMCs shows the fast drug release compared to other SEMCs. Further, KMG6 SEMCs also exhibited 5.12-fold higher relative intestinal serosal fluid absorption compared to crystalline ITZ. The pharmacokinetic parameters such Cmax, AUC and Tmax of KMG6 SEMCs significantly improved compared to crystalline ITZ. In conclusion, the manipulation of ITZ solubility, dissolution rate and absorption using SEMCs is a promising strategy for bioavailability enhancement.

Copernicus for urban resilience in Europe.

The urban community faces a significant obstacle in effectively utilising Earth Observation (EO) intelligence, particularly the Copernicus EO program of the European Union, to address the multifaceted aspects of urban sustainability and bolster urban resilience in the face of climate change challenges. In this context, here we present the efforts of the CURE project, which received funding under the European Union's Horizon 2020 Research and Innovation Framework Programme, to leverage the Copernicus Core Services (CCS) in supporting urban resilience. CURE provides spatially disaggregated environmental intelligence at a local scale, demonstrating that CCS can facilitate urban planning and management strategies to improve the resilience of cities. With a strong emphasis on stakeholder engagement, CURE has identified eleven cross-cutting applications between CCS that correspond to the major dimensions of urban sustainability and align with user needs. These applications have been integrated into a cloud-based platform known as DIAS (Data and Information Access Services), which is capable of delivering reliable, usable and relevant intelligence to support the development of downstream services towards enhancing resilience planning of cities throughout Europe.

Loratadine oral bioavailability enhancement via solid dispersion loaded oro-dispersible films: Formulation, characterization and pharmacokinetics.

Loratadine (LRD) belongs to second-generation tricyclic H1 antihistamine class, known for its non-sedating properties in allergic reactions. H1 antihistamines avoid and block the responses to allergens or histamine in nose and conjunctivae, thereby abolishing itching, congestion and sneezing. LRD is a Biopharmaceutical Class System (BCS) class II drug with dissolution or solubility limited absorption which limited the oral bioavailability and therapeutic efficacy of LRD. To improve the oral bioavailability of LRD for allergic disease (urticaria) treatment, LRD solid dispersions (LRD-SDs) were integrating into oro-dispersible films (ODFs). LRD-SDs were prepared through hot-melt extrusion method (HME) using d-alpha-tocopherol polyethylene glycol 1000 succinate (TPGS-1000), and polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (SP). Subsequently, LRD-SDs were incorporated in ODFs by solvent casting method. The physicochemical and mechanical properties of LRD solid dispersions-loaded oro-dispersible films (LRD-SDs-ODFs), were evaluated. The in-vitro dissolution, ex-vivo permeation, oral bioavailability, and pharmacodynamics studies were conducted to evaluate LRD-SDs-ODFs efficiency. LRD-SDs-ODFs showed superior solubility and in-vitro dissolution results compared to that of pure LRD (p < 0.05). The solubility of the LRD-SD coded as LTS-4 was 190 times higher than the pure drug in aqueous media. The average hydrodynamic particle size (PS), polydispersity index (PDI), and zeta potential (ZP) of SD particles were 76 ± 2.1 nm, 0.20 ± 0.08 and - 19.16 ± 1.4 mV, respectively. Moreover, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) results confirmed the amorphousness of LRD in LRD-SDs-ODFs. The permeability flux of LRD was 44.6 ± 3.1 µg/cm2/h from DPF-5 formulation. Likewise, in vivo oral bioavailability of DPF-5 in Sprague-Dawley rats was significantly increased (p < 0.05) compared to free LRD. Further, wheal area was reduced 20 % higher than LRD in 8 h (p < 0.05). Overall, LRD-SDs-ODFs considerably enhanced LRD solubility, dissolution rate, bioavailability, and antihistaminic efficacy. Our findings show that SDs-ODFs is an effective carrier system for delivering poorly soluble LRD.

Biomass-derived carbon deposited TiO2 nanotube photocatalysts for enhanced hydrogen production.

In this study, titanium oxide nanotubes (TiO2NTs) were deposited on the surface of activated carbon (AC) by varying the wt% of AC. The physicochemical properties of synthesized TiO2NTs-AC nanocomposites were analysed by various characterization techniques such as XRD, FT-IR, Raman, DRUV-vis, HR-TEM, XPS, PL, and N2 physisorption. The FT-IR, EDX, and XPS analyses proved the existence of interaction between AC and TiO2NTs. This study found that as the content of AC increases, the surface area and pore volume increase while the energy bandgap decreases. The TiO2NTs-AC nanocomposite with 40% AC exhibited a surface area of 291 m2 g-1, pore volume of 0.045 cm3 g-1 and half pore width = 8.4 Å and had a wide band gap energy (3.15 eV). In addition, the photocatalytic application of the prepared nanocomposites for photocatalytic H2 production was investigated. The H2 was produced via photo-reforming in the presence of a sacrificial agent (methanol) under sunlight irradiation. It was found that the prepared TiO2NTs-AC nanocomposite with 40% AC acted as an efficient photocatalyst for aqueous-methanol reforming under various optimization conditions. Approximately 18 000 µmol-1 hydrogen gas was produced via aqueous-methanol reforming under optimized conditions (catalyst dose = 100 mg, temperature = 25 °C, time = 12 hours, vol. of methanol = 20% (v/v), and pH = 7). The reusability of the TiO2NTs-AC nanocomposite was also investigated for 5 consecutive cycles, and the results suggested only a slight decline in efficiency even after the fifth cycle. This study demonstrates the ability of an activated carbon deposited TiO2NT catalyst to produce hydrogen effectively under sunlight.

Selective Thermal and Photocatalytic Decomposition of Aqueous Hydrazine to Produce H2 over Ag-Modified TiO2 Nanomaterial.

An Ag-modified TiO2 nanomaterial was prepared by a one-pot synthesis method using tetra butyl titanate, silver nitrate, and sodium hydroxide in water at 473 K for 3 h. X-ray diffraction, scanning electron microscopy, and transmission electron microscopy were used to determine the structure and morphology of the synthesized Ag-modified TiO2 nanomaterial. The diffuse reflectance UV-visible and photoluminescence spectroscopy results revealed that metallic Ag nanoparticles decreased the optical band gap and photoluminescence intensity of the TiO2. In addition, the Raman peak intensity and absorbance were increased after Ag modification onto TiO2. The photocatalytic efficiency of the synthesized samples was tested for decomposition of aqueous hydrazine solution under visible light irradiation. The photocatalytic efficiency of Ag-modified TiO2 nanomaterials was higher than that of bare TiO2 and Ag metal NPs due to the synergistic effect between the Ag metal and TiO2 structures. In addition, the surface plasmon resonance (SPR) electron transfer from Ag metal particles to the conduction band of TiO2 is responsible for superior activity of TiO2-Ag catalyst. The Ag-modified TiO2 nanomaterials offered a 100% H2 selectivity within 30 min of reaction time and an apparent rate constant of 0.018 min-1 with an activation energy of 34.4 kJ/mol under visible light radiation.

Eco-Friendly Sustainable Nanocarriers to Treat Oxidative Stresses and Skin Aging-Related Ailments, Valorization of a By-Product.

The peel from Citrus-sinensis L. is a medicinally significant food waste, and its extract (O-Ext) could be significant against oxidative stresses and skin aging, However, the penetration barriers, instability in formulation, undefined toxicities, and enzymatic activities make the O-Ext difficult to formulate and commercialize. The goal of this study was to evaluate O-Ext against oxidative stress, prepare O-Ext-loaded nano-lipid carriers (O-NLCs), and load them into topical O/W-emulsion (O-NLC-E) to improve O-Ext permeation and its in vivo antiaging effects. TPC, TFC, DPPH activity, and mineral/metal contents of O-Ext were determined via atomic-absorption spectroscopy. For bioactive compounds profiling, GC-MS analysis was carried out. O-NLCs were prepared and tested for physicochemical attributes, while HaCaT and fibroblast cells were used to study permeation and cytotoxicity. The kinetic characteristics of ex vivo permeation through rat skin were established, following the Higuchi model. Following written consent, safety investigations were conducted on human volunteers for three months, where optimized O-NLC-E and B-NLC-E were regularly applied on cheeks. Non-invasive procedures were used to assess the volunteer's skin erythema, TEWL, sebum level, melanin, hydration, pH, elasticity, and pore sizes after specified intervals. The results demonstrated that applying O-NLC-E formulation to the skin of volunteers directed significant antiaging benefits. The study offers nanotechnology-based sustainability approach against skin ageing.

E-Commerce Policy and International Business.

The rise of digitization and information and communication technologies (ICT) is playing a vital role in facilitating global trade and business activities and in overcoming cross-border transaction costs. In so doing, it offers firms significant benefits and opportunities to compete on a global scale, as witnessed during the ongoing COVID-19 pandemic. The growth and widespread diffusion of internet-enabled technologies and platforms have created numerous opportunities for firms to provide products and services across both developed and developing markets. Yet, limited research has been conducted in the international business domain to explore the rise of ecommerce and its implications for international business scholarship. In this focused issue, we present an examination of the role played by e-commerce in international business, paying particular attention to the policy aspect of e-commerce and issuing a call for a greater integration of e-commerce policy in international business research.

Fabrication of chitosan-MnO2­iridium/nanoceria supported nanoparticles: Catalytic and anti-radical activities.

Chitosan capped MnO2­iridium nanoparticles supported on nanoceria (Ch-MnO2-Ir/CeO2) were fabricated by using combination of colloidal solution and metal displacement galvanic methods. The oxidative degradation of acid orange 7 in aqueous solution by activated persulfate with the as-prepared nanoparticles was studied. The resulting Ch-MnO2-Ir/CeO2 with S2O82-, 80 % degraded 70.06 mg/L of acid orange 7 within 100 min, while at the same time, Ch-Ir, Ch-MnO2, and Ch-Ir-MnO2 remained inactive. CeO2 increased the surface of the catalyst, and also improved the reactive oxygen species site of Ch-Ir-MnO2 through the activation of S2O82- with CeO2. The reversible redox cycle reaction, Ce (III) ↔ Ce (IV) and strong synergistic effect of MnO2-Ir are responsible for the remarkable catalytic performance of Ch-MnO2-Ir/CeO2/S2O82- system. The degradation of acid orange 7 could be significantly retarded with inorganic (NO3- < Cl- < SO42- < H2PO4- < HCO3-) and organic scavengers (ethanol < tertiary butanol < benzoquinone < phenol). Ch-MnO2-Ir/CeO2 exhibited excellent stability and reusability. Anti-radical activity of chitosan and Ch-MnO2-Ir/CeO2 was evaluated with 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical. The free radical properties increase with concentration of chitosan and Ch-MnO2-Ir/CeO2.

Detecting fake news and disinformation using artificial intelligence and machine learning to avoid supply chain disruptions.

Fake news and disinformation (FNaD) are increasingly being circulated through various online and social networking platforms, causing widespread disruptions and influencing decision-making perceptions. Despite the growing importance of detecting fake news in politics, relatively limited research efforts have been made to develop artificial intelligence (AI) and machine learning (ML) oriented FNaD detection models suited to minimize supply chain disruptions (SCDs). Using a combination of AI and ML, and case studies based on data collected from Indonesia, Malaysia, and Pakistan, we developed a FNaD detection model aimed at preventing SCDs. This model based on multiple data sources has shown evidence of its effectiveness in managerial decision-making. Our study further contributes to the supply chain and AI-ML literature, provides practical insights, and points to future research directions.

In Vitro and Ex Vivo Evaluation of Mangifera indica L. Extract-Loaded Green Nanoparticles in Topical Emulsion against Oxidative Stress and Aging.

Although Mangifera indica L. extract (M-Ext) of the peel and kernel possesses potent antioxidant and excellent antiaging qualities, the effects are only partially seen because of the skin's limited ability to absorb it. M-Ext was loaded into nanolipid carriers (M-NLCs) in this work to create a green topical formulation that would boost antiaging efficacy and address penetration deficit. Compound identification was done using GCMS and atomic absorption spectroscopy for heavy metals in M-Ext. M-Ext was also evaluated against oxidative stress antioxidant enzymes. The M-NLCs were fabricated and evaluated for their physicochemical characterizations. Cytotoxicity and cell permeation analysis of M-Ext and M-NLCs were carried out in fibroblasts and HaCaT cell lines. An ex vivo permeation study of M-Ext and M-NLC-loaded emulsion was performed through rat skin and the kinetic parameters were determined. Kinetic data showed that the ex vivo permeation of M-NLC-loaded emulsion through rat skin followed the Higuchi model. The safety profile was evaluated in human volunteers after written consent. Three months' in vivo investigations were conducted using the optimized M-NLC-loaded emulsion and vehicle (B-NLC-loaded emulsion) on human cheeks for comparison. The volunteers' skin erythema level, melanin contents, TEWL index, moisture contents, sebum level, elasticity, pH, and pore size were examined after the first, second, and third month via noninvasive techniques. There were significant findings for physicochemical characterizations and in vitro and ex vivo studies. The findings demonstrate that the green nanolipid carriers amplified the overall antioxidant effectiveness and may represent an emerging treatment strategy for oxidative stresses and aging.

Hypomorphic GINS3 variants alter DNA replication and cause Meier-Gorlin syndrome.

The eukaryotic CDC45/MCM2-7/GINS (CMG) helicase unwinds the DNA double helix during DNA replication. The GINS subcomplex is required for helicase activity and is, therefore, essential for DNA replication and cell viability. Here, we report the identification of 7 individuals from 5 unrelated families presenting with a Meier-Gorlin syndrome-like (MGS-like) phenotype associated with hypomorphic variants of GINS3, a gene not previously associated with this syndrome. We found that MGS-associated GINS3 variants affecting aspartic acid 24 (D24) compromised cell proliferation and caused accumulation of cells in S phase. These variants shortened the protein half-life, altered key protein interactions at the replisome, and negatively influenced DNA replication fork progression. Yeast expressing MGS-associated variants of PSF3 (the yeast GINS3 ortholog) also displayed impaired growth, S phase progression defects, and decreased Psf3 protein stability. We further showed that mouse embryos homozygous for a D24 variant presented intrauterine growth retardation and did not survive to birth, and that fibroblasts derived from these embryos displayed accelerated cellular senescence. Taken together, our findings implicate GINS3 in the pathogenesis of MGS and support the notion that hypomorphic variants identified in this gene impaired cell and organismal growth by compromising DNA replication.

Physicochemical Characterizations and Pharmacokinetic Evaluation of Pentazocine Solid Lipid Nanoparticles against Inflammatory Pain Model.

Pentazocine (PTZ), a narcotic-antagonist analgesic, has been extensively used in the treatment of initial carcinogenic or postoperative pain. Hepatic first-pass metabolism results in low oral bioavailability and high dose wastage. Herein, 10 mg (-)-Pentazocine (HPLC-grade) was incorporated to solid lipid nanoparticles (SLNs) using a double water-oil-water (w/o/w) emulsion by solvent emulsification-evaporation technique, followed by high shear homogenization to augment its oral bioavailability, considering the lymphatic uptake. The resulting SLNs were characterized for zeta potential (ZP), particle size (PS), and polydispersity index (PDI) using a zetasizer. The entrapment efficiency (EE) and loading capacity (LC) were calculated. Chemical interactions, through the identification of active functional groups, were assessed by Fourier-transformed infrared (FTIR) spectroscopy. The nature (crystallinity) of the SLNs was determined by X-ray diffractometry (XRD). The surface morphology was depicted by transmission electron microscopy (TEM). In vitro (in Caco-2 cells) and in vivo (in male Wistar rats) investigations were carried out to evaluate the PTZ release behavior and stability, as well as the cellular permeation, cytotoxicity, systemic pharmacokinetics, antinociceptive, anti-inflammatory, and antioxidative activities of PTZ-loaded SLNs, mainly compared to free PTZ (marketed conventional dosage form). The optimized PTZ-loaded SLN2 showed significantly higher in vitro cellular permeation and negligible cytotoxicity. The in vivo bioavailability and pharmacokinetics parameters (t1/2, Cmax) of the PTZ-loaded SLNs were also significantly improved, and the nociception and inflammation, following carrageenan-induced inflammatory pain, were markedly reduced. Concordantly, PTZ-loaded SLNs showed drastic reduction in the oxidative stress (e.g., malonaldehyde (MDA)) and proinflammatory cytokines (e.g., Interleukin (IL)-1ß, -6, and TNF-α). The histological features of the paw tissue following, carrageenan-induced inflammation, were significantly improved. Taken together, the results demonstrated that PTZ-loaded SLNs can improve the bioavailability of PTZ by bypassing the hepatic metabolism via the lymphatic uptake, for controlled and sustained drug delivery.

Reimagining global food value chains through effective resilience to COVID-19 shocks and similar future events: A dynamic capability perspective.

The restructuring of global value/supply chains gained increasing attention as the unprecedented COVID-19 echoed around the world. Yet, the COVID-19 related theory-driven, large scale quantitative, and empirical studies are relatively scarce. This study advances the extant literature by empirically investigating how do firms in the global food value chains (GFVCs) re-imagine their businesses structure in response to the COVID-19-becoming more resilient and competitive to the current pandemic and similar future events. We leverage a unique data of 231 senior managers of the Australian GFVCs and examine their firms' response strategies. Drawing upon key insights from the dynamic capability view, we find that GFVCs' competitiveness is achieved when exposure to COVID-19 shocks elicits dynamic capabilities-readiness, response, recovery-and these capabilities work jointly and sequentially to cultivate resilience. A key finding of this study is that firms with domestic plus global value chain partners are more resilient than those having only global business partners. This finding implies that excessive reliance on offshoring sometimes becomes lethal, especially amid unexpected and prolonged global shocks and, therefore, companies should strike a balance between domestic and global business partners to remain competitive. These findings offer important contributions to theory, practice, and UN sustainable development goals.

Chitosan capped trimetallic nanoparticles: Synthesis and their Congo red adsorbing activities.

Chitosan capped Fe0-based Fe-Pd-Ir (Chi-Fe-Pd-Ir) tri-metallic nanoparticles were fabricated using metal displacement method in presence of sodium borohydride. The preliminary indications of Fe0 production were the appearance of pale yellow color with ferric nitrate, NaBH4, and chitosan. Chitosan was detected by using ninhydrin color test, thermal gravimetric analysis and measurement of relative viscosity. The average molecular weight of chitosan and Chi-Fe-Pd-Ir decreased with increased potassium persulfate concentration. Chi-Fe-Pd-Ir used as an adsorbent for the removal of Congo red. The sorption equilibrium data were fitted into Langmuir, Freundlich, Temkin, and Dubinin-Radushkevich isotherms (DRK). The maximum monolayer adsorption capacity (Q0max), and sorption intensity (n) were estimated to be 93.4 mg/g and 2.0, respectively, from Langmuir and Freundlich adsorption isotherm models. The mean free energy was calculated by using DRK isotherm to be 0.15 kJ/mol. Sorption parameters indicate that the Congo red adsorbed on the surface of Chi-Fe-Pd-Ir through monolayer formation via physisorption process. The adsorption of CR on Chi-Fe-Pd-Ir was in good agreement with the Langmuir adsorption isotherm and pseudo-second-order kinetic model. Protonated amino group of chitosan was also responsible for the adsorption of anionic CR along with the Fe-Pd-Ir NPs.

Two Promising Anti-Cancer Compounds, 2-Hydroxycinnaldehyde and 2- Benzoyloxycinnamaldehyde: Where do we stand?

Natural bioactive compounds with anti-carcinogenic activity are gaining tremendous interest in the field of oncology. Cinnamon, an aromatic condiment commonly used in tropical regions, appeared incredibly promising as an adjuvant for cancer therapy. Indeed, its whole or active parts (e.g., bark, leaf) exhibited significant anti-carcinogenic activity, which is mainly due to two cinnamaldehyde derivatives, namely 2-hydroxycinnaldehyde (HCA) and 2- benzoyloxycinnamaldehyde (BCA). In addition to their anti-cancer activity, HCA and BCA exert immunomodulatory, anti-platelets, and anti-inflammatory activities. The highly reactive α,ßunsaturated carbonyl pharmacophore, called Michael acceptor, contributes to their therapeutic effects. The molecular mechanisms underlying their anti-tumoral and anti-metastatic effects are miscellaneous, strongly suggesting that these compounds are multi-targeting compounds. Nevertheless, unravelling the exact molecular mechanisms of HCA and BCA remains a challenging matter which is necessary for optimal controlled-drug targeting delivery, safety, and efficiency. Eventually, their poor pharmacological properties (e.g., systemic bioavailability and solubility) represent a limitation and depend both on their administration route (e.g., per os, intravenously) and the nature of the formulation (e.g., free, smart nano-). This concise review focused on the potential of HCA and BCA as adjuvants in cancer. We describe their medicinal effects as well as provide an update about their molecular mechanisms reported either in-vitro, ex-vivo, or in animal models.