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1.
Viruses ; 14(2)2022 01 21.
Article in English | MEDLINE | ID: covidwho-1715755

ABSTRACT

The interaction of phages with abiotic environmental surfaces is usually an understudied field of phage ecology. In this study, we investigated the virucidal potential of different metal salts, metal and ceramic powders doped with Ag and Cu ions, and newly fabricated ceramic and metal surfaces against Phi6 bacteriophage. The new materials were fabricated by spark plasma sintering (SPS) and/or selective laser melting (SLM) techniques and had different surface free energies and infiltration features. We show that inactivation of Phi6 in solutions with Ag and Cu ions can be as effective as inactivation by pH, temperature, or UV. Adding powder to Ag and Cu ion solutions decreased their virucidal effect. The newly fabricated ceramic and metal surfaces showed very good virucidal activity. In particular, 45%TiO2 + 5%Ag + 45%ZrO2 + 5%Cu, in addition to virus adhesion, showed virucidal and infiltration properties. The results indicate that more than 99.99% of viruses deposited on the new ceramic surface were inactivated or irreversibly attached to it.


Subject(s)
Bacteriophage phi 6/drug effects , Copper/pharmacology , Silver/pharmacology , Bacteriophage phi 6/growth & development , Bacteriophage phi 6/physiology , Ceramics/chemistry , Copper/chemistry , Hydrogen-Ion Concentration , Powders/chemistry , Silver/chemistry , Surface Properties , Temperature
2.
Int J Pharm ; 614: 121457, 2022 Feb 25.
Article in English | MEDLINE | ID: covidwho-1616526

ABSTRACT

Dry powder inhalation therapy has been shown to be an effective method for treating respiratory diseases like asthma, Chronic Obstructive Pulmonary Diseases and Cystic Fibrosis. It has also been widely accepted and used in clinical practices. Such success has led to great interest in inhaled therapy on treating systemic diseases in the past two decades. The current coronavirus (COVID-19) pandemic also has increased such interest and is triggering more potential applications of dry powder inhalation therapy in vaccines and antivirus drugs. Would the inhaled dry powder therapy on systemic disorders be as encouraging as expected? This paper reviews the marketed and in-development dry powder inhaler (DPI) products on the treatment of systemic diseases, their status in clinical trials, as well as the potential for COVID-19 treatment. The advancements and unmet problems on DPI systems are also summarized. With countless attempts behind and more challenges ahead, it is believed that the dry powder inhaled therapy for the treatment of systemic disorders still holds great potential and promise.


Subject(s)
COVID-19 , Administration, Inhalation , COVID-19/drug therapy , Dry Powder Inhalers , Humans , Powders , SARS-CoV-2
3.
Pharm Res ; 39(1): 115-141, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1588758

ABSTRACT

MOTIVATION: With the coronavirus pandemic still raging, prophylactic-nasal and early-treatment throat-sprays could help prevent infection and reduce viral load. Niclosamide has the potential to treat a broad-range of viral infections if local bioavailability is optimized as mucin-penetrating solutions that can reach the underlying epithelial cells. EXPERIMENTAL: pH-dependence of supernatant concentrations and dissolution rates of niclosamide were measured in buffered solutions by UV/Vis-spectroscopy for niclosamide from different suppliers (AK Sci and Sigma), as precipitated material, and as cosolvates. Data was compared to predictions from Henderson-Hasselbalch and precipitation-pH models. Optical-microscopy was used to observe the morphologies of original, converted and precipitated niclosamide. RESULTS: Niclosamide from the two suppliers had different polymorphs resulting in different dissolution behavior. Supernatant concentrations of the "AKSci-polymorph" increased with increasing pH, from 2.53µM at pH 3.66 to 300µM at pH 9.2, reaching 703µM at pH 9.63. However, the "Sigma-polymorph" equilibrated to much lower final supernatant concentrations, reflective of more stable polymorphs at each pH. Similarly, when precipitated from supersaturated solution, or as cosolvates, niclosamide also equilibrated to lower final supernatant concentrations. Polymorph equilibration though was avoided by using a solvent-exchange technique to make the solutions. CONCLUSIONS: Given niclosamide's activity as a host cell modulator, optimized niclosamide solutions could represent universal prophylactic nasal and early treatment throat sprays against COVID19, its more contagious variants, and other respiratory viral infections. They are the simplest and potentially most effective formulations from both an efficacy standpoint as well as manufacturing and distribution, (no cold chain). They now just need testing.


Subject(s)
Antiviral Agents/administration & dosage , Antiviral Agents/chemistry , COVID-19/drug therapy , Mucins/drug effects , Niclosamide/administration & dosage , Niclosamide/chemistry , Virus Diseases/drug therapy , Administration, Intranasal , Aerosols , Biological Availability , Chemistry, Pharmaceutical , Drug Compounding , Humans , Hydrogen-Ion Concentration , Pharynx , Powders , Solubility , Viral Load
4.
Int J Pharm ; 608: 121122, 2021 Oct 25.
Article in English | MEDLINE | ID: covidwho-1433361

ABSTRACT

Herein, we demonstrated the development and characterization of a dry powder inhaler (DPI) formulation of edoxaban (EDX); and investigated the in-vitro anticoagulation effect for the management of pulmonary or cerebral coagulopathy associated with COVID-19 infection. The formulations were prepared by mixing the inhalable micronized drug with a large carrier lactose and dispersibility enhancers, leucine, and magnesium stearate. The drug-excipient interaction was studied using X-Ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) methods. The drug and excipients showed no physical inter particulate interaction. The in-vitro drug aerosolization from the developed formulation was determined by a Twin Stage Impinger (TSI) at a flow rate of 60 ± 5 L /min. The amount of drug deposition was quantified by an established HPLC-UV method. The fine particle fraction (FPF) of EDX API from drug alone formulation was 7%, whereas the formulations with excipients increased dramatically to almost 7-folds up to 47%. The developed DPI formulation of EDX showed a promising in-vitro anticoagulation effect at a very low concentration. This novel DPI formulation of EDX could be a potential and effective inhalation therapy for managing pulmonary venous thromboembolism (VTE) associated with COVID-19 infection. Further studies are warranted to investigate the toxicity and clinical application of the inhaled EDX DPI formulation.


Subject(s)
Blood Coagulation Disorders/drug therapy , COVID-19 , Dry Powder Inhalers , Pyridines/administration & dosage , Thiazoles/administration & dosage , Administration, Inhalation , Aerosols , Blood Coagulation Disorders/virology , COVID-19/complications , Humans , Particle Size , Powders
5.
Molecules ; 26(16)2021 Aug 06.
Article in English | MEDLINE | ID: covidwho-1376914

ABSTRACT

Sea buckthorn (Hippophae rhamnoides L. (HR)) leaf powders are the underutilized, promising resource of valuable compounds. Genotype and processing methods are key factors in the preparation of homogenous, stable, and quantified ingredients. The aim of this study was to evaluate the phenolic, triterpenic, antioxidant profiles, carotenoid and chlorophyll content, and chromatic characteristics of convection-dried and freeze-dried HR leaf powders obtained from ten different female cultivars, namely 'Avgustinka', 'Botaniceskaja Liubitelskaja', 'Botaniceskaja', 'Hibrid Percika', 'Julia', 'Nivelena', 'Otradnaja', 'Podarok Sadu', 'Trofimovskaja', and 'Vorobjovskaja'. The chromatic characteristics were determined using the CIELAB scale. The phytochemical profiles were determined using HPLC-PDA (high performance liquid chromatography with photodiode array detector) analysis; spectrophotometric assays and antioxidant activities were investigated using ABTS (2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)) and FRAP (ferric ion reducing antioxidant power) assays. The sea buckthorn leaf powders had a yellowish-green appearance. The drying mode had a significant impact on the total antioxidant activity, chlorophyll content, and chromatic characteristics of the samples; the freeze-dried samples were superior in antioxidant activity, chlorophyll, carotenoid content, and chromatic profile, compared to convection-dried leaf powder samples. The determined triterpenic and phenolic profiles strongly depend on the cultivar, and the drying technique had no impact on qualitative and quantitative composition. Catechin, epigallocatechin, procyanidin B3, ursolic acid, α-amyrin, and ß-sitosterol could be used as quantitative markers in the phenolic and triterpenic profiles. The cultivars 'Avgustinka', 'Nivelena', and 'Botaniceskaja' were superior to other tested cultivars, with the phytochemical composition and antioxidant activity.


Subject(s)
Antioxidants/chemistry , Antioxidants/pharmacology , Desiccation , Hippophae/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Plant Leaves/chemistry , Powders
6.
Pharmacol Res ; 161: 105126, 2020 11.
Article in English | MEDLINE | ID: covidwho-1318945

ABSTRACT

BACKGROUND: With the global epidemic of coronavirus disease (COVID-19), China has made progress in the prevention and control of the epidemic, and traditional Chinese medicine (TCM) has played a key role in dealing with the disease's effects on the respiratory system. This randomized controlled clinical trial evaluated the clinical efficacy and prognosis of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules in patients with COVID-19. METHODS: A total of 283 patients participated in this clinical trial, and participants were randomly assigned to receive either 1) Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules or 2) Linahua granules, both combined with western medicine, or 3) western medicine alone for 14 days. At the end of the trial, the improvement and resolution rates of clinical symptoms and the rate of patients who progressed to severe disease status were evaluated. RESULTS: After 14 days of treatment, there was no significant difference in the improvement rate of clinical symptoms among the three groups (P > 0.05). Huoxiang Zhengqi dropping pills combined with Lianhua Qingwen granules has advantages in the treatment of nausea, vomiting and limb soreness. During treatment, all participants were treated with western medicine, and there was a significant difference in the use of macrolides among the three groups (P < 0.05). Specifically, the utilization rate of antibiotics in the western medicine group was significantly greater than that of the other two groups. Among the 182 diagnosed patients who completed this clinical trial, 13 patients progressed to severe disease, including one case in the Huoxiang + Lianhua group (1.6 %), five cases in the Lianhua group (8.6 %), and seven cases in the western medicine group (11.1 %). There was no statistical differences in this rate among the three groups (P > 0.05). However, the proportion of patients who progressed to severe disease in the Huoxiang + Lianhua group was the lowest, suggesting that the combination of TCM with western medicine has a potential advantage in improving the prognosis of patients with COVID-19. CONCLUSION: The use of Huoxiang Zhengqi dropping pills and Lianhua Qingwen granules combined with western medicine may have clinical advantages for COVID-19 patients in improving clinical symptoms, reducing utilization rate of anti-infective drugs, and improving patient prognosis, which could pave the way for the use of complementary medicine in treating this infection.


Subject(s)
COVID-19/drug therapy , Drugs, Chinese Herbal/therapeutic use , Adult , Aged , COVID-19/complications , COVID-19/diagnosis , China , Disease Progression , Drugs, Chinese Herbal/administration & dosage , Female , Humans , Male , Medicine, Chinese Traditional , Middle Aged , Myalgia/drug therapy , Myalgia/etiology , Nausea/drug therapy , Nausea/etiology , Powders , Tablets , Treatment Outcome , Vomiting/drug therapy , Vomiting/etiology
7.
Mult Scler Relat Disord ; 54: 103148, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1316592

ABSTRACT

BACKGROUND: Upon the COVID-19 pandemic emergence, safety concerns and logistic drawbacks stimulated the search for alternatives to pulse therapy at infusion centres to treat multiple sclerosis relapses. OBJECTIVE: To describe our experience treating multiple sclerosis relapses with a dilute injectable methylprednisolone powder orally administered, in a safe home-based environment and with totally virtual assessment and follow up via telemedicine. METHODS: Descriptive observational, retrospective, single-centre, open label, study in the real-world setting. RESULTS: Between August 2020 and March 2021, ten multiple sclerosis patients and one neuromyelitis optica spectrum disease patient, regularly assisted at our multiple sclerosis centre in Argentina, experienced twelve disease relapses (nine moderate/severe relapses and three mild relapses) and were treated with the oral dilute of injectable methylprednisolone powder pulses with good efficacy as well as adequate tolerance and safety profile. CONCLUSIONS: The oral pulse therapy based on the methylprednisolone powder dilution we describe is simple and comfortable to administer and can be an option in countries like Argentina, where the oral methylprednisolone formulation is not marketed. In these pandemic times, a home based and virtually monitored pulse therapy could represent a safe and effective alternative to manage relapses while minimizing the patient's risk of exposure to SARS-CoV-2.


Subject(s)
COVID-19 , Multiple Sclerosis , Neuromyelitis Optica , Administration, Oral , Humans , Injections, Intravenous , Methylprednisolone/therapeutic use , Multiple Sclerosis/drug therapy , Neuromyelitis Optica/drug therapy , Pandemics , Powders/therapeutic use , Recurrence , Retrospective Studies , SARS-CoV-2 , Water
8.
Int J Pharm ; 603: 120701, 2021 Jun 15.
Article in English | MEDLINE | ID: covidwho-1225261

ABSTRACT

In this work, we have developed and tested a dry powder form of niclosamide made by thin-film freezing (TFF) and administered it by inhalation to rats and hamsters to gather data about its toxicology and pharmacokinetics. Niclosamide, a poorly water-soluble drug, is an interesting drug candidate because it was approved over 60 years ago for use as an anthelmintic medication, but recent studies demonstrated its potential as a broad-spectrum antiviral with pharmacological effect against SARS-CoV-2 infection. TFF was used to develop a niclosamide inhalation powder composition that exhibited acceptable aerosol performance with a fine particle fraction (FPF) of 86.0% and a mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) of 1.11 µm and 2.84, respectively. This formulation not only proved to be safe after an acute three-day, multi-dose tolerability and exposure study in rats as evidenced by histopathology analysis, and also was able to achieve lung concentrations above the required IC90 levels for at least 24 h after a single administration in a Syrian hamster model. To conclude, we successfully developed a niclosamide dry powder inhalation that overcomes niclosamide's limitation of poor oral bioavailability by targeting the drug directly to the primary site of infection, the lungs.


Subject(s)
COVID-19 , Niclosamide , Administration, Inhalation , Aerosols , Animals , Cricetinae , Dry Powder Inhalers , Freezing , Humans , Particle Size , Powders , Rats , SARS-CoV-2
9.
Eur J Pharm Biopharm ; 163: 198-211, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1174210

ABSTRACT

Oral inhalation is the preferred route for delivery of small molecules to the lungs, because high tissue levels can be achieved shortly after application. Biologics are mainly administered by intravenous injection but inhalation might be beneficial for the treatment of lung diseases (e.g. asthma). This review discusses biological and pharmaceutical challenges for delivery of biologics and describes promising candidates. Insufficient stability of the proteins during aerosolization and the biological environment of the lung are the main obstacles for pulmonary delivery of biologics. Novel nebulizers will improve delivery by inducing less shear stress and administration as dry powder appears suitable for delivery of biologics. Other promising strategies include pegylation and development of antibody fragments, while carrier-encapsulated systems currently play no major role in pulmonary delivery of biologics for lung disease. While development of various biologics has been halted or has shown little effects, AIR DNase, alpha1-proteinase inhibitor, recombinant neuraminidase, and heparin are currently being evaluated in phase III trials. Several biologics are being tested for the treatment of coronavirus disease (COVID)-19, and it is expected that these trials will lead to improvements in pulmonary delivery of biologics.


Subject(s)
Lung Diseases/drug therapy , Lung/drug effects , Peptides/administration & dosage , Proteins/administration & dosage , Administration, Inhalation , Administration, Oral , Animals , Biological Products/administration & dosage , Drug Carriers/chemistry , Drug Delivery Systems/methods , Humans , Nebulizers and Vaporizers , Powders/administration & dosage
10.
Complement Ther Clin Pract ; 42: 101297, 2021 Feb.
Article in English | MEDLINE | ID: covidwho-977991

ABSTRACT

OBJECTIVE: This review aimed at systematically evaluating the efficacy and safety of Yinqiao powder combined with western medicine in the treatment of pneumonia. METHODS: A systematic search for randomized controlled trials (RCTs) focusing on pneumonia treatment using a combination of Yinqiao powder and western medicine was performed in PubMed, the Cochrane Library, EMBASE, Web of Science, CNKI, Wanfang, Weipu (VIP) and CBM. The retrieval time limit was from the establishment of the database to June 2020. Two researchers independently screened the literature, extracted the data and evaluated the bias risk of the included studies. A meta-analysis was performed using RevMan5.3 software. Quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULT: Fifteen RCTs involving 1705 patients were included in the analysis. The meta-analysis results revealed the total effective rate of the treatment group [RR = 1.21, 95% CI (1.15, 1.27), P < 0.00001], bacterial clearance rate [RR = 1.13, 95% CI (1.05, 1.22), P = 0.001], adverse reactions [RR = 0.54, 95% CI (0.38, 0.76), P = 0.0005]. There were statistically significant differences in the cooling time, T cell number, procalcitonin (PCT) and C-reactive protein (CRP) value decline rate (P < 0.05). There was no statistically significant difference in the decline rate of neutrophils and leukocytes (P > 0.05). CONCLUSION: The current evidence indicated that the Yinqiao powder combined with western medicine can improve total efficiency in the treatment of pneumonia patients. The combination therapy performed better when compared to western medicine alone in the cooling time, bacterial clearance rate, T cell count, decline rates of CRP and PCT as well as in the incidences of adverse reactions. However, there was no significant difference in the decline rates of neutrophils and leucocytes between the two groups. The funnel plot, Egger's test and Begg's test indicated publication bias, which may be associated with unpublished negative study results. Due to the limitation of the quality and quantity of the included studies, more high-quality studies should be performed to verify our conclusions.


Subject(s)
Drugs, Chinese Herbal , Medicine , Pneumonia , Child , Drugs, Chinese Herbal/adverse effects , Humans , Pneumonia/drug therapy , Powders
11.
Carbohydr Polym ; 264: 118011, 2021 Jul 15.
Article in English | MEDLINE | ID: covidwho-1172080

ABSTRACT

Veklury™ by Gilead Sciences, Inc., containing antiviral drug, remdesivir (REM) has received emergency authorization in the USA and in Europe for COVID-19 therapy. Here, for the first time, we describe details of the non-covalent, host-guest type interaction between REM and the solubilizing excipient, sulfobutylether-beta-cyclodextrin (SBECD) that results in significant solubility enhancement. Complete amorphousness of the cyclodextrin-enabled REM formulation was demonstrated by X-ray diffraction, thermal analysis, Raman chemical mapping and electron microscopy/energy dispersive spectroscopy. The use of solubilizing carbohydrate resulted in a 300-fold improvement of the aqueous solubility of REM, and enhanced dissolution rate of the drug enabling the preparation of stable infusion solutions for therapy. 2D ROESY NMR spectroscopy provided information on the nature of REM-excipient interaction and indicated the presence of inclusion phenomenon and the electrostatic attraction between anionic SBECD and nitrogen-containing REM in aqueous solution.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Excipients/chemistry , beta-Cyclodextrins/chemistry , Adenosine Monophosphate/chemistry , Alanine/chemistry , Antiviral Agents/chemistry , COVID-19/drug therapy , Calorimetry, Differential Scanning , Freeze Drying/methods , Magnetic Resonance Spectroscopy , Microscopy, Electron, Scanning , Molecular Docking Simulation , Nanofibers/chemistry , Powders , Solubility , Spectrum Analysis, Raman , X-Ray Diffraction
12.
ACS Appl Mater Interfaces ; 13(14): 16084-16096, 2021 Apr 14.
Article in English | MEDLINE | ID: covidwho-1164786

ABSTRACT

As COVID-19 exemplifies, respiratory diseases transmitted through aerosols or droplets are global threats to public health, and respiratory protection measures are essential first lines of infection prevention and control. However, common face masks are single use and can cause cross-infection due to the accumulated infectious pathogens. We developed salt-based formulations to coat membrane fibers to fabricate antimicrobial filters. Here, we report a mechanistic study on salt-induced pathogen inactivation. The salt recrystallization following aerosol exposure was characterized over time on sodium chloride (NaCl), potassium sulfate (K2SO4), and potassium chloride (KCl) powders and coatings, which revealed that NaCl and KCl start to recrystallize within 5 min and K2SO4 within 15 min. The inactivation kinetics observed for the H1N1 influenza virus and Klebsiella pneumoniae matched the salt recrystallization well, which was identified as the main destabilizing mechanism. Additionally, the salt-coated filters were prepared with different methods (with and without a vacuum process), which led to salt coatings with different morphologies for diverse applications. Finally, the salt-coated filters caused a loss of pathogen viability independent of transmission mode (aerosols or droplets), against both DI water and artificial saliva suspensions. Overall, these findings increase our understanding of the salt-recrystallization-based technology to develop highly versatile antimicrobial filters.


Subject(s)
Filtration/instrumentation , Influenza A Virus, H1N1 Subtype/drug effects , Klebsiella pneumoniae/drug effects , Masks , Potassium Chloride/chemistry , Sodium Chloride/chemistry , Sulfates/chemistry , Aerosols , Air Filters , Crystallization , Kinetics , Membranes, Artificial , Polypropylenes , Powders , Respiratory Protective Devices , Temperature , X-Ray Diffraction
13.
Expert Rev Anti Infect Ther ; 19(10): 1325-1330, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1147907

ABSTRACT

Objectives: Bney Brak city tops Israel's COVID-19 infection rate and mortality. Before the Jewish New Year (two-day gathering) SARS-CoV-2 PCR positivity rates were 17.6% and reached 28.1% two weeks later Taffix - an innovative nasal powder creates a protective gel over the nasal mucosa blocking viruses from infecting nasal cells, was tested for efficacy in preventing SARS CoV2 infection.Methods: In a prospective users survey, 243 members of an ultra-orthodox community that participated in two days prayers were followed for 14 days following this 'superspread' event. Eighty-three used Taffix throughout holiday's prayers and the following two weeks (ITT). Eighty-one used it regularly (PP). Two used it rarely if at all. The remaining 160 did not use Taffix.Results: After 14 days, 0/81 (0%) of (PP) Tafffix users, 2/83 (2.4%) of (ITT) Taffix users and 16/160 (10%) nonusers were infected. Odds ratio for infection among Taffix users was 0.22, a reduction of 78% (95%CI 1%-95%). No side effects reported.Conclusion: Taffix could be an additional tool against COVID19 spread, in addition to recommended safety measures. This is the first time that a prevention measure of SARS-CoV-2, beyond the use of masks, has proved effective.


Subject(s)
COVID-19/prevention & control , Endemic Diseases/prevention & control , Hypromellose Derivatives/therapeutic use , Administration, Intranasal , Adolescent , Adult , COVID-19/epidemiology , Female , Humans , Hypromellose Derivatives/administration & dosage , Israel/epidemiology , Male , Medication Adherence , Middle Aged , Nasal Sprays , Powders , Prospective Studies , SARS-CoV-2 , Young Adult
14.
Lett Appl Microbiol ; 72(6): 725-729, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1096912

ABSTRACT

There does not appear to be any studies in the published literature on the stability of SARS-CoV-2 in climbing chalk powder (magnesium carbonate and/or calcium carbonate), which has been hypothesized to pose a potential risk of fomite transmission of coronavirus disease 2019 (COVID-19) within climbing gyms. The aim of this study was to determine the infectivity of a model human coronavirus HCoV-OC43 in the presence of climbing chalk powder on a dry plastic surface. The stability of HCoV-OC43 on a plastic surface dusted with climbing chalk powders (magnesium carbonate, calcium carbonate or a blended chalk) was determined by titration on BHK-21 fibroblast cells. No chalk and no virus controls were included. HCoV-OC43 was stable on the plastic surface for 48 h. The stability of HCoV-OC43 was significantly (P ≤ 0·05) reduced in the presence of magnesium carbonate, calcium carbonate and the chalk blend; the infectivity was reduced by ≥2·29 log10 50% tissue culture infective dose (TCID50 ) immediately upon on contact and by ≥2·46 log10 TCID50 within 1 h of contact. These findings suggest that the infectivity of coronaviruses is reduced by climbing chalk, limiting the risk of potential fomite transmission.


Subject(s)
Coronavirus OC43, Human/drug effects , Animals , Calcium Carbonate , Cell Line , Coronavirus OC43, Human/pathogenicity , Cricetinae , Fibroblasts/drug effects , Fibroblasts/virology , Fomites , Powders
15.
J Aerosol Med Pulm Drug Deliv ; 34(1): 20-31, 2021 02.
Article in English | MEDLINE | ID: covidwho-1066217

ABSTRACT

Background: Hydroxychloroquine (HCQ) is one of the repurposed drugs proposed for the treatment of coronavirus disease 2019 (COVID-19). However, all the published clinical trials involve oral administration of the drug, although the disease is primarily a respiratory one. Direct inhaled delivery could reduce the side effects associated with oral use and ensure a high concentration of the drug in the lungs. In this study, inhalable HCQ powders were prepared and characterized for potential COVID-19 therapy. Methods: Hydroxychloroquine sulfate (HCQ-sul) was jet milled (JM) followed by conditioning by storage at different relative humidities (43%, 53%, 58%, and 75% RHs) for 7 days. The solid-state properties, including particle morphology and size distribution, crystallinity, and vapor moisture profiles of HCQ-sul samples, were characterized by scanning electron microscopy, laser diffraction, X-ray powder diffraction, differential scanning calorimetry, thermogravimetric analysis, and dynamic water vapor sorption. The aerosol performance of the HCQ-sul powders was assessed using a medium-high resistance Osmohaler coupling to a next-generation impactor (NGI) at a flow rate of 60 L/min. Results: The jet-milled powder showed a volume median diameter of 1.7 µm (span 1.5) and retained the same crystalline form as the raw HCQ-sul. A small amount of amorphous materials was present in the jet-milled HCQ-sul, which was convertible to the stable, crystalline state after conditioning at 53%, 58%, and 75% RH. The recovered fine particle fraction (FPF)recovered and the emitted fine particle fraction (FPFemitted) of the HCQ-sul sample immediately after jet milling and the samples after conditioning at 43%, 53%, and 58% RH were similar at ∼43% and 61%, respectively. In contrast, the sample having conditioned at 75%RH showed lower corresponding values at 33% and 26% respectively, due to the formation of solid bridges caused by excessive moisture. Conclusion: Inhalable crystalline powders of HCQ-sul were successfully prepared, which can be used for clinical testing as a potential inhaled COVID-19 treatment.


Subject(s)
COVID-19/drug therapy , Hydroxychloroquine/administration & dosage , SARS-CoV-2 , Administration, Inhalation , Calorimetry, Differential Scanning , Humans , Particle Size , Powders , X-Ray Diffraction
16.
Environ Res ; 192: 110274, 2021 01.
Article in English | MEDLINE | ID: covidwho-837150

ABSTRACT

Despite the COVID-19 pandemic and wearing masks in many countries, women are keen on elegance, beauty and the use of face foundations. Assessment of health risks associated with the regular use of face foundation by females is dynamic due to the emerging products. The most common international 14 brands of face foundation powders were collected and the concentrations of different elements (Ag, Al, As, B, Ba, Be, Ca, Cd, Co, Cr, Cu, Fe, Hg, K, Li, Mg, Mn, Mo, Na, P, Pb, Sb, Se, Sn, V and Zn) in each sample were determined. A combined approach merging the conventional and computational tools was used for investigating the risk of exposure to toxic elements. Monte Carlo simulations were applied to calculate risks associated with twenty elements. We attempted different probability distribution functions for concentrations because the actual distribution functions are not known, and the only data available are the mean value and standard deviation of concentrations obtained from experiment. Our results indicate that the total non-carcinogenic health risk through exposure to different elements (Hazardous Index, HI) does not strongly depend on the choice of the probability distribution function for the concentrations. We also show that taking into account probability distributions of other variables and parameters such as body weight, exposed skin area, skin adhesion, etc. does not significantly change the main result rather just slightly broadening the final Hazardous Index distribution function. We found that calculated HI is well below unity for all considered samples, i.e., the dermal exposure to toxic elements in the considered facial powders is negligible and the considered face foundation powders are quite safe to use.


Subject(s)
COVID-19 , Trace Elements , Female , Humans , Pandemics , Powders , Risk Assessment , SARS-CoV-2
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