Cepharanthine Dry Powder Inhaler for the Treatment of Acute Lung Injury.

Severe acute respiratory syndrome Coronavirus 2 (SARS-CoV-2) induces a severe cytokine storm that may cause acute lung injury/acute respiratory distress syndrome (ALI/ARDS) with high clinical morbidity and mortality in infected individuals. Cepharanthine (CEP) is a bisbenzylisoquinoline alkaloid isolated and extracted from Stephania cepharantha Hayata. It exhibits various pharmacological effects, including antioxidant, anti-inflammatory, immunomodulatory, anti-tumor, and antiviral activities. The low oral bioavailability of CEP can be attributed to its poor water solubility. In this study, we utilized the freeze-drying method to prepare dry powder inhalers (DPI) for the treatment of acute lung injury (ALI) in rats via pulmonary administration. According to the powder properties study, the aerodynamic median diameter (Da) of the DPIs was 3.2 µm, and the in vitro lung deposition rate was 30.26; thus, meeting the Chinese Pharmacopoeia standard for pulmonary inhalation administration. We established an ALI rat model by intratracheal injection of hydrochloric acid (1.2 mL/kg, pH = 1.25). At 1 h after the model's establishment, CEP dry powder inhalers (CEP DPIs) (30 mg/kg) were sprayed into the lungs of rats with ALI via the trachea. Compared with the model group, the treatment group exhibited a reduced pulmonary edema and hemorrhage, and significantly reduced content of inflammatory factors (TNF-α, IL-6 and total protein) in their lungs (p < 0.01), indicating that the main mechanism of CEP underlying the treatment of ALI is anti-inflammation. Overall, the dry powder inhaler can deliver the drug directly to the site of the disease, increasing the intrapulmonary utilization of CEP and improving its efficacy, making it a promising inhalable formulation for the treatment of ALI.

Enhancing Biocidal Capability in Cuprite Coatings.

The SARS-CoV-2 global pandemic has reinvigorated interest in the creation and widespread deployment of durable, cost-effective, and environmentally benign antipathogenic coatings for high-touch public surfaces. While the contact-kill capability and mechanism of metallic copper and its alloys are well established, the biocidal activity of the refractory oxide forms remains poorly understood. In this study, commercial cuprous oxide (Cu2O, cuprite) powder was rapidly nanostructured using high-energy cryomechanical processing. Coatings made from these processed powders demonstrated a passive "contact-kill" response to Escherichia coli (E. coli) bacteria that was 4× (400%) faster than coatings made from unprocessed powder. No viable bacteria (>99.999% (5-log10) reduction) were detected in bioassays performed after two hours of exposure of E. coli to coatings of processed cuprous oxide, while a greater than 99% bacterial reduction was achieved within 30 min of exposure. Further, these coatings were hydrophobic and no external energy input was required to activate their contact-kill capability. The upregulated antibacterial response of the processed powders is positively correlated with extensive induced crystallographic disorder and microstrain in the Cu2O lattice accompanied by color changes that are consistent with an increased semiconducting bandgap energy. It is deduced that cryomilling creates well-crystallized nanoscale regions enmeshed within the highly lattice-defective particle matrix. Increasing the relative proportion of lattice-defective cuprous oxide exposed to the environment at the coating surface is anticipated to further enhance the antipathogenic capability of this abundant, inexpensive, robust, and easily handled material for wider application in contact-kill surfaces.

Synthesis of the first remdesivir cocrystal: design, characterization, and therapeutic potential for pulmonary delivery.

While cocrystal engineering is an emerging formulation strategy to overcome drug delivery challenges, its therapeutic potential in non-oral applications remains not thoroughly explored. We herein report for the first time the successful synthesis of a cocrystal for remdesivir (RDV), an antiviral drug with broad-spectrum activities against RNA viruses. The RDV cocrystal was prepared with salicylic acid (SA) via combined liquid-assisted grinding (LAG) and thermal annealing. Formation of RDV-SA was found to be a thermally activated process, where annealing at high temperature after grinding was a prerequisite to facilitate the cocrystal growth from an amorphous intermediate, rendering it elusive under ambient preparing conditions. Through powder X-ray analysis with Rietveld refinement, the three-dimensional molecular structure of RDV-SA was resolved. The thermally annealed RDV-SA produced by LAG crystalized in a non-centrosymmetric monoclinic space group P21 with a unit cell volume of 1826.53(17) Å3, accommodating one pair of RDV and SA molecules in the asymmetric unit. The cocrystal formation was also characterized by differential scanning calorimetry, solid-state nuclear magnetic resonance, and Fourier-transform infrared spectroscopy. RDV-SA was further developed as inhaled dry powders by spray drying for potential COVID-19 therapy. The optimized RDV-SA dry powders exhibited a mass median aerodynamic diameter of 4.33 ± 0.2 µm and fine particle fraction of 41.39 ± 4.25 %, indicating the suitability for pulmonary delivery. Compared with the raw RDV, RDV-SA displayed a 15.43-fold higher fraction of release in simulated lung fluid at 120 min (p = 0.0003). RDV-SA was safe in A549 cells without any in vitro cytotoxicity observed in the RDV concentration from 0.05 to 10 µM.

Review on Generation and Characterization of Copper Particles and Copper Composites Prepared by Mechanical Milling on a Lab-Scale.

This review aims to expose mechanical milling as an alternative method for generating copper-based particles (copper particles (CuP) and copper composites (CuC)); more specifically, via a top-down or bottom-up approach, on a lab-scale. This work will also highlight the different parameters that can affect the size distribution, the type, and the morphology of the obtained CuP or CuC, such as the type of mechanical mill, ball-to-powder ratios (BPR), the milling speed, milling time, and the milling environment, among others. This review analyzes various papers based on the Cu-based particle generation route, which begins with a pretreatment step, then mechanical milling, its approach (top-down or bottom-up), and the post-treatment. Finally, the characterization methods of the resulting CuP and CuC through mechanical milling are also discussed.

The effectiveness of chlorine dioxide gas in portable personal disinfectants to inhibit bacterial growth.

Disinfectants, especially air disinfectants, are necessary to prevent the potential spread of pathogens (bacteria and viruses) in the pandemic era and minimize the spread of pathogens. Some of the commercial disinfectant products that are often used generally contain chlorine dioxide (ClO2) gas. This study tested the effectiveness of two different commercial disinfectants, a liquid stick disinfectant and a powder disinfection card, to carry out the disinfection of pathogenic bacteria in the environment. These two disinfectants were used as a medium for releasing chlorine dioxide gas which has a much stronger bactericidal effect. In the form of liquid stick, ClO2 is more effective in the disinfection process rather than in the form of powder. The effectiveness of the liquid disinfectant in inhibiting the growth of pathogenic bacteria is influenced by the temperature and the area of the open space covered. Considering that the release from both disinfectants used is very small (0.002 ppmv/h), it takes a small area to ensure that the disinfection process runs effectively.

Neutralisation of SARS-CoV-2 by monoclonal antibody through dual targeting powder formulation.

Neutralising monoclonal antibody (mAb) is an important weapon in our arsenal for combating respiratory viral infections. However, the effectiveness of neutralising mAb has been impeded by the rapid emergence of mutant variants. Early administration of broad-spectrum mAb with improved delivery efficiency can potentially enhance efficacy and patient outcomes. WKS13 is a humanised mAb which was previously demonstrated to exhibit broad-spectrum activity against SARS-CoV-2 variants. In this study, a dual targeting formulation strategy was designed to deliver WKS13 to both the nasal cavity and lower airways, the two critical sites of infection caused by SARS-CoV-2. Dry powders of WKS13 were first prepared by spray drying, with cyclodextrin used as stabiliser excipient. Two-fluid nozzle (TFN) was used to produce particles below 5 µm for lung deposition (C-TFN formulation) and ultrasonic nozzle (USN) was used to produce particles above 10 µm for nasal deposition (C-USN formulation). Gel electrophoresis and size exclusion chromatography studies showed that the structural integrity of mAb was successfully preserved with no sign of aggregation after spray drying. To achieve dual targeting property, C-TFN and C-USN were mixed at various ratios. The aerosolisation property of the mixed formulations dispersed from a nasal powder device was examined using a Next Generation Impactor (NGI) coupled with a glass expansion chamber. When the ratio of C-TFN in the mixed formulation increased, the fraction of particles deposited in the lung increased proportionally while the fraction of particles deposited in the nasal cavity decreased correspondingly. A customisable aerosol deposition profile could therefore be achieved by manipulating the mixing ratio between C-TFN and C-USN. Dual administration of C-TFN and C-USN powders to the lung and nasal cavity of hamsters, respectively, was effective in offering prophylactic protection against SARS-CoV-2 Delta variant. Viral loads in both the lung tissues and nasal wash were significantly reduced, and the efficacy was comparable to systemic administration of unformulated WKS13. Overall, dual targeting powder formulation of neutralising mAb is a promising approach for prophylaxis of respiratory viral infections. The ease and non-invasive administration of dual targeting nasal powder may facilitate the widespread distribution of neutralising mAb during the early stage of unpredictable outbreaks.

Inhalable Nanoparticle-based Dry Powder Formulations for Respiratory Diseases: Challenges and Strategies for Translational Research.

The emergence of novel respiratory infections (e.g., COVID-19) and expeditious development of nanoparticle-based COVID-19 vaccines have recently reignited considerable interest in designing inhalable nanoparticle-based drug delivery systems as next-generation respiratory therapeutics. Among various available devices in aerosol delivery, dry powder inhalers (DPIs) are preferable for delivery of nanoparticles due to their simplicity of use, high portability, and superior long-term stability. Despite research efforts devoted to developing inhaled nanoparticle-based DPI formulations, no such formulations have been approved to date, implying a research gap between bench and bedside. This review aims to address this gap by highlighting important yet often overlooked issues during pre-clinical development. We start with an overview and update on formulation and particle engineering strategies for fabricating inhalable nanoparticle-based dry powder formulations. An important but neglected aspect in in vitro characterization methodologies for linking the powder performance with their bio-fate is then discussed. Finally, the major challenges and strategies in their clinical translation are highlighted. We anticipate that focused research onto the existing knowledge gaps presented in this review would accelerate clinical applications of inhalable nanoparticle-based dry powders from a far-fetched fantasy to a reality.

Development of an IgY-Based Treatment to Control Bovine Coronavirus Diarrhea in Dairy Calves.

Bovine Coronavirus (BCoV) is a major pathogen associated with neonatal calf diarrhea. Standard practice dictates that to prevent BCoV diarrhea, dams should be immunized in the last stage of pregnancy to increase BCoV-specific antibody (Ab) titers in serum and colostrum. For the prevention to be effective, calves need to suck maternal colostrum within the first six to twelve hours of life before gut closure to ensure a good level of passive immunity. The high rate of maternal Ab transfer failure resulting from this process posed the need to develop alternative local passive immunity strategies to strengthen the prevention and treatment of BCoV diarrhea. Immunoglobulin Y technology represents a promising tool to address this gap. In this study, 200 laying hens were immunized with BCoV to obtain spray-dried egg powder enriched in specific IgY Abs to BCoV on a large production scale. To ensure batch-to-batch product consistency, a potency assay was statistically validated. With a sample size of 241, the BCoV-specific IgY ELISA showed a sensitivity and specificity of 97.7% and 98.2%, respectively. ELISA IgY Abs to BCoV correlated with virus-neutralizing Ab titers (Pearson correlation, R2 = 0.92, p < 0.001). Most importantly, a pilot efficacy study in newborn calves showed a significant delay and shorter duration of BCoV-associated diarrhea and shedding in IgY-treated colostrum-deprived calves. Calves were treated with milk supplemented with egg powder (final IgY Ab titer to BCoV ELISA = 512; VN = 32) for 14 days as a passive treatment before a challenge with BCoV and were compared to calves fed milk with no supplementation. This is the first study with proof of efficacy of a product based on egg powder manufactured at a scale that successfully prevents BCoV-associated neonatal calf diarrhea.

Protein Aggregates in Inhaled Biologics: Challenges and Considerations.

Pulmonary delivery is the main route of administration for treatment of local lung diseases. Recently, the interest in delivery of proteins through the pulmonary route for treatment of lung diseases has significantly increased, especially after Covid-19 pandemic. The development of an inhalable protein combines the challenges of inhaled as well as biologic products since protein stability may be compromised during manufacture or delivery. For instance, spray drying is the most common technology for manufacture of inhalable biological particles, however, it imposes shear and thermal stresses which may cause protein unfolding and aggregation post drying. Therefore, protein aggregation should be evaluated for inhaled biologics as it could impact the safety and/or efficacy of the product. While there is extensive knowledge and regulatory guidance on acceptable limits of particles, which inherently include insoluble protein aggregates, in injectable proteins, there is no comparable knowledge for inhaled ones. Moreover, the poor correlation between in vitro setup for analytical testing and the in vivo lung environment limits the predictability of protein aggregation post inhalation. Thus, the purpose of this article is to highlight the major challenges facing the development of inhaled proteins compared to parenteral ones, and to share future thoughts to resolve them.

Dry powder formulation of azithromycin for COVID-19 therapeutics.

Azithromycin is an antibiotic proposed as a treatment for the coronavirus disease 2019 (COVID-19) due to its immunomodulatory activity. The aim of this study is to develop dry powder formulations of azithromycin-loaded poly(lactic-co-glycolic acid) (PLGA) nanocomposite microparticles for pulmonary delivery to improve the low bioavailability of azithromycin. Double emulsion method was used to produce nanoparticles, which were then spray dried to form nanocomposite microparticles. Encapsulation efficiency and drug loading were analysed, and formulations were characterised by particle size, zeta potential, morphology, crystallinity and in-vitro aerosol dispersion performance. The addition of chitosan changed the neutrally-charged azithromycin only formulation to positively-charged nanoparticles. However, the addition of chitosan also increased the particle size of the formulations. It was observed in the NGI® data that there was an improvement in dispersibility of the chitosan-related formulations. It was demonstrated in this study that all dry powder formulations were able to deliver azithromycin to the deep lung regions, which suggested the potential of using azithromycin via pulmonary drug delivery as an effective method to treat COVID-19.

Dry Powder Inhaler with the technical and practical obstacles, and forthcoming platform strategies.

A Dry Powder Inhaler (DPI) is a technique as well as a device used to inhale formulation which is in the form of dry powder, and is inhaled through the nose or mouth. It was developed for the purpose of treating conditions like chronic obstructive pulmonary disease (COPD), Asthma, and even cystic fibrosis etc. The aim of the review is to discuss the different methods of preparation of dry powders along with the characterization of DPI. Here we present the outline of different methods like supercritical fluid extraction (SCF), spray drying, and milling. The review focussed on various devices including single and multi-dose devices used in the DPI. It also highlights on recent advances in the DPI including nano particulate system, siRNA-based medication, liposomes, and pro-liposomes based delivery. In COVID-19 silver nanoparticles-based DPIs provide very prominent results in the infected lungs. Moreover, this review states that the AI-based DPI development provides and improvement in the bioavailability and effectiveness of the drug along with the role of artificial neural networks (ANN). The study also showed that nasally administered drugs (nose to brain) can easily cross the blood-brain barrier (BBB) and enter the central nervous system (CNS) through the olfactory and trigeminal pathway which provides effective CNS concentrations at lower dosage. It is suggested that DPIs not only target respiratory complications but also treat CNS complications too. This review provides support and guides the researcher in the recent development and evaluation of DPI.

Tolerability and pharmacokinetic evaluation of inhaled dry powder hydroxychloroquine in healthy volunteers.

RATIONALE: Inhaled antimicrobials enable high local concentrations where needed and, compared to orally administration, greatly reduce the potential for systemic side effects. In SARS-CoV-2 infections, hydroxychloroquine sulphate (HCQ) administered as dry powder via inhalation could be safer than oral HCQ allowing higher and therefore more effective pulmonary concentrations without dose limiting toxic effects. OBJECTIVES: To assess the local tolerability, safety and pharmacokinetic parameters of HCQ inhalations in single ascending doses of 5, 10 and 20 mg using the Cyclops dry powder inhaler. METHODS: Twelve healthy volunteers were included in the study. Local tolerability and safety were assessed by pulmonary function tests, electrocardiogram and recording adverse events. To estimate systemic exposure, serum samples were collected before and 0.5, 2 and 3.5 h after inhalation. RESULTS AND DISCUSSION: Dry powder HCQ inhalations were well tolerated by the participants, except for transient bitter taste in all participants and minor coughing irritation. There was no significant change in QTc-interval or drop in FEV1 post inhalation. The serum HCQ concentration remained below 10 µg/L in all samples. CONCLUSION: Single doses of inhaled dry powder HCQ up to 20 mg are safe and well tolerated. Our data support that further studies with inhaled HCQ dry powder to evaluate pulmonary pharmacokinetics and efficacy are warranted.

Preparation and Characterization of Inhalable Ivermectin Powders as a Potential COVID-19 Therapy.

Background: Ivermectin has received worldwide attention as a potential COVID-19 treatment after showing antiviral activity against SARS-CoV-2 in vitro. However, the pharmacokinetic limitations associated with oral administration have been postulated as limiting factors to its bioavailability and efficacy. These limitations can be overcome by targeted delivery to the lungs. In this study, inhalable dry powders of ivermectin and lactose crystals were prepared and characterized for the potential treatment of COVID-19. Methods: Ivermectin was co-spray dried with lactose monohydrate crystals and conditioned by storage at two different relative humidity points (43% and 58% RH) for a week. The in vitro dispersion performance of the stored powders was examined using a medium-high resistance Osmohaler connecting to a next-generation impactor at 60 L/min flow rate. The solid-state characteristics including particle size distribution and morphology, crystallinity, and moisture sorption profiles of raw and spray-dried ivermectin samples were assessed by laser diffraction, scanning electron microscopy, Raman spectroscopy, X-ray powder diffraction, thermogravimetric analysis, differential scanning calorimetry, and dynamic vapor sorption. Results: All the freshly spray-dried formulation (T0) and the conditioned samples could achieve the anticipated therapeutic dose with fine particle dose of 300 µg, FPF_recovered of 70%, and FPF_emitted of 83%. In addition, the formulations showed a similar volume median diameter of 4.3 µm and span of 1.9. The spray-dried formulations were stable even after conditioning and exposing to different RH points as ivermectin remained amorphous with predominantly crystalline lactose. Conclusion: An inhalable and stable dry powder of ivermectin and lactose crystals was successfully formulated. This powder inhaler ivermectin candidate therapy appears to be able to deliver doses that could be safe and effective to treat the SARS-COV-2 infection. Further development of this therapy is warranted.

In vitro inhibition of SARS-CoV-2 Infection by dry algae powders.

Chlorella spp., Spirulina spp., and fucoidan dry powders, are commercialized as food supplements and are considered safe for human consumption. Their broad-spectrum antiviral properties have been studied, however, their effect against SARS-CoV-2 remains unknown. We investigated the potential antiviral activity of three algae powders: Chlorella vulgaris, Arthrospira maxima (Spirulina) and fucoidan purified from marine brown algae Sargassum spp. against SARS-CoV-2 infection in vitro. Vero cells were incubated with 70 µg/ml of each algae powder and either 50 or 100 TCID50/ml of SARS-CoV-2, in two types of experiments (pretreatment and simultaneous) and comparing two kinds of solvents (DMEM and DMSO). Chlorella vulgaris powder, inhibited SARS-CoV-2 infection in all assays; viral RNA was significantly reduced in supernatants at 24, 48, 72, and 96 h post-infection, the highest difference in viral load (8000-fold) was observed after 96 h. Arthrospira maxima powder inhibited SARS-CoV-2 infection using 50 TCID50/ml for both experimental schemes, but protection percent was lower when viral inoculum was increase to 100 TCID50/ml; viral RNA decreased 48 h after infection, reaching a 250-fold difference at 72 h. Fucoidan powder partially inhibited SARS-CoV-2 infection since no CPE was observed in 62.5% of trated cultures in DMEM, but the antiviral activity was increased to 100% of protection when DMSO was used as solvent. All the algae samples showed high antiviral activity against SARS-CoV-2 with a SI above of 18. These results suggest that all three algae samples are potential therapeutic candidates for the treatment of COVID-19.

Recent developments in lactose blend formulations for carrier-based dry powder inhalation.

Lactose is the most commonly used excipient in carrier-based dry powder inhalation (DPI) formulations. Numerous inhalation therapies have been developed using lactose as a carrier material. Several theories have described the role of carriers in DPI formulations. Although these theories are valuable, each DPI formulation is unique and are not described by any single theory. For each new formulation, a specific development trajectory is required, and the versatility of lactose can be exploited to optimize each formulation. In this review, recent developments in lactose-based DPI formulations are discussed. The effects of varying the material properties of lactose carrier particles, such as particle size, shape, and morphology are reviewed. Owing to the complex interactions between the particles in a formulation, processing adhesive mixtures of lactose with the active ingredient is crucial. Therefore, blending and filling processes for DPI formulations are also reviewed. While the role of ternary agents, such as magnesium stearate, has increased, lactose remains the excipient of choice in carrier-based DPI formulations. Therefore, new developments in lactose-based DPI formulations are crucial in the optimization of inhalable medicine performance.

The Effect of Short Treatment with Nigella Sativa on Symptoms, the Cluster of Differentiation (CD) Profile, and Inflammatory Markers in Mild COVID-19 Patients: A Randomized, Double-Blind Controlled Trial.

The current study investigated the impact of different doses of Nigella sativa seeds on the symptoms, the cluster of differentiation profile group, and inflammatory markers of mild COVID-19 cases. METHODS: The study was a double-blind placebo-controlled clinical trial. Patients with mild and asymptomatic SARS-CoV-2 infection patients were randomly subdivided into seven subgroups: Group (GP) 1: received charcoal capsules as a control group, and GP 2: received three capsules of whole Nigella sativa seeds daily, two capsules in the morning and one in the evening; GP 3: received three capsules of whole Nigella sativa seeds every 12 h, GP 4: received five capsules in the morning and four capsules of whole Nigella sativa seeds in the evening, GP 5: received one capsule of Nigella sativa powder every 12 h; GP 6: received two capsules of Nigella sativa powder every 12 h; GP 7: received three capsules of Nigella sativa powder every 12 h; all treatment course was for ten days. Inflammatory parameters were assessed before and after interventions. RESULTS: 262 subjects were included in the final analysis. No significant difference was detected regarding age, gender, and nationality. No significant differences were detected between the inflammatory marker in all groups. The WBCs showed a significant difference between before and after the intervention. While for procalcitonin, a significant difference was demonstrated in groups 1,4, and 6. CONCLUSIONS: The current randomized clinical trial did not reveal a significant effect of ten days of treatment with various doses of Nigella sativa on symptoms, differentiation profile, and inflammatory markers of patients with COVID-19. As a natural product, the effect of Nigella sativa on disease requires weeks to manifest itself.

Protein and carbohydrate content of infant formula purchased in the United States.

BACKGROUND: The protein and carbohydrate composition of formula fed infants' diets in the United States (US) has not been described. The aims of this study were to characterize these dietary exposures in infant formula purchased in the US and to estimate the proportion of formula purchased which is hypoallergenic or lactose-reduced formula. METHODS: Powdered infant formula purchase data from all major physical stores in the US prior to the COVID-19 pandemic, between 2017 and 2019, were obtained from Information Resources, Inc. Protein and carbohydrate composition and scoop sizes for each formula were obtained from manufacturers. Ready to feed liquid products, products for premature infants and products for over 1 year old were not included. RESULTS: Total volumes of term formula purchased were 216 million kg of formula powder (equivalent to 1.65 billion litres) over 3 years. Intact protein formula was 67.9% of formula purchased, 26.6% was partially hydrolysed and 5.5% was hypoallergenic (5.2% extensively hydrolysed protein; 0.3% amino acid based). Soy protein formula represented 5.1% of formula purchased. Carbohydrate content overall was 52.7% lactose, 42.3% glucose polymers and 5.0% sucrose. 23.7% of formula purchased included sucrose as a carbohydrate. Of all formula purchased, 59.0% was lactose reduced, containing a non-lactose carbohydrate. Of 'standard' formula, defined as intact protein, non-thickened, cow's milk formula, 32.3% was lactose reduced. The proportion of hypoallergenic formula purchased significantly exceeded the prevalence of cow's milk protein allergy and increased over the 3-year study period from 4.9% to 7.6% of all formula sold. CONCLUSIONS: US infants are exposed to unnecessarily high levels of non-lactose carbohydrates and hypoallergenic formula, and this may represent a significant nutritional health risk.

A novel and water-soluble material for coronavirus inactivation from oseltamivir in the cavity of methyl and sulfated-ß-cyclodextrins through inclusion complexation.

A potentially active water-soluble anti-viral with lesser toxic material from the Oseltamivir (OTV) has been produced by the sonication method. The formed material has been further characterized by UV-visible, FT-IR, powder XRD, SEM, TGA/DTA, ROESY, XPS, AFM and etc., The results of DFT calculation have proven that inclusion complexes (ICs) are theoretically and energetically more advantageous models and structures have also been proposed based on the results. Analysis of drug release has been carried out at three pH levels, and it is revealed the analysis is most helpful at acidic pH levels for the ICs with S-CD over H-CD. Over OTV without CDs, OTV:S-CD-ICs exhibited a very less cytotoxic ability on cancer cell lines than ICs with M-CD. ICs enhanced the coronavirus inactivation nature of OTV. This study provides for the first time a full characterization of ICs of OTV with CDs and highlights the impact of complexation on pharmacological activity.

The effects of nutrition bio-shield superfood powder on immune system function: A clinical trial study among patients with COVID-19.

The present study aimed to evaluate the effects of Nutrition Bio-shield Superfood (NBS) powder on the immune system function and clinical manifestations in patients with COVID-19. We compare the effects of NBS powder on the immune system function and clinical manifestations among two different groups: 1) intervention group receiving standard treatment scheduled according to treatment guidelines plus NBS powder, and 2) control group receiving only the same standard treatment. The serum levels of IL-2, IL-6, IL-17, IFNγ, and TNFα were determined after four weeks of treatment by specific ELISA kits according to the manufacturer's instructions. Finally, the level of immune system stimulation and inflammatory markers were compared at baseline and after intervention in both groups. Data were analyzed using SPSS (version 22). A p-value of ≤ 0.05 was set as significant. A total of 47 patients with COVID-19 (24 patients in the intervention group and 23 patients in the control group) were included in this study. Results showed that the differences in the mean decrease of IL-2, IL-6, and TNF-α in the intervention group in comparison to the control group were 0.93, 10.28, and 8.11 pg/ml, respectively (P<0.001). On the other hand, there was no difference in IL-17, IFNγ, monocytes, eosinophil, and other inflammatory indices between the intervention and control groups. Although NBS powder was able to significantly decrease the levels of some proinflammatory cytokines in patients with COVID-19, however, it is noteworthy that the course of the disease was to large part unaffected by NBS power and there was a reduction independent of treatment. The present study indicates that NBS powder could provide a beneficial anti-inflammatory effect in patients with COVID-19. Hence, NBS in treating patients with COVID-19 shows promise as an adjuvant to the current standard antiviral treatment of such patients. Clinical Trial Registration: https://www.irct.ir, identifier IRCT20200426047206N1.

Debulking different Corona (SARS-CoV-2 delta, omicron, OC43) and Influenza (H1N1, H3N2) virus strains by plant viral trap proteins in chewing gums to decrease infection and transmission.

Because oral transmission of SARS-CoV-2 is 3-5 orders of magnitude higher than nasal transmission, we investigated debulking of oral viruses using viral trap proteins (CTB-ACE2, FRIL) expressed in plant cells, delivered through the chewing gum. In omicron nasopharyngeal (NP) samples, the microbubble count (based on N-antigen) was significantly reduced by 20 µg of FRIL (p < 0.0001) and 0.925 µg of CTB-ACE2 (p = 0.0001). Among 20 delta or omicron NP samples, 17 had virus load reduced below the detection level of spike protein in the RAPID assay, after incubation with the CTB-ACE2 gum powder. A dose-dependent 50% plaque reduction with 50-100 ng FRIL or 600-800 µg FRIL gum against Influenza strains H1N1, H3N2, and Coronavirus HCoV-OC43 was observed with both purified FRIL, lablab bean powder or gum. In electron micrographs, large/densely packed clumps of overlapping influenza particles and FRIL protein were observed. Chewing simulator studies revealed that CTB-ACE2 release was time/dose-dependent and release was linear up to 20 min chewing. Phase I/II placebo-controlled, double-blinded clinical trial (IND 154897) is in progress to evaluate viral load in saliva before or after chewing CTB-ACE2/placebo gum. Collectively, this study advances the concept of chewing gum to deliver proteins to debulk oral viruses and decrease infection/transmission.