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2.
J Environ Sci Health A Tox Hazard Subst Environ Eng ; 57(11): 970-976, 2022.
Article in English | MEDLINE | ID: covidwho-2087557

ABSTRACT

The main goal of this study is to compare concentrations of atmospheric Hg(p) for various particles sizes Total Suspended Particulates (TSP), PM18, PM10, PM2.5, PM1, PM<1 before (2018-2019) and during (2019-2020 and 2020-2021) COVID-19 occurred periods in central Taiwan. In addition, test the statistical differences concentrations of Hg(p) for various particles sizes before and during COVID-19 occurred periods in central Taiwan. Finally, calculate the Hg(p) health risk assessment before and during COVID-19 occurred period in central Taiwan.The result indicated that the mean Hg(p) concentrations in TSP and PM2.5 were higher during (2020-2021) the COVID-19 occurred period than that of the mean Hg(p) concentrations in TSP and PM2.5 before the COVID-19 occurred period. In addition, the Hg(p)concentrations PM18, PM10, PM2.5, PM1 and PM<1 were all increased during the COVID-19 occurred period. The Hg(p) concentrations in TSP were decreased during (2019-2020) the COVID-19 occurred period when compared with that of the before the COVID-19 occurred period. Moreover, significant mean Hg(p) concentrations differences were existed at PM18, PM10 and PM2.5 before and during (2020-2021) COVID-19 occurred periods. Finally, the HQ and HI values for Hg(p) were both increased during COVID-19 occurred periods when compared with before COVID-19 occurred period in this study.


Subject(s)
Air Pollutants , COVID-19 , Mercury , Humans , Air Pollutants/analysis , Particle Size , Environmental Monitoring , COVID-19/epidemiology , Taiwan/epidemiology , Mercury/analysis , Dust , Particulate Matter/analysis , Seasons
3.
Sci Total Environ ; 838(Pt 4): 156516, 2022 Sep 10.
Article in English | MEDLINE | ID: covidwho-2082807

ABSTRACT

The worldwide restrictions of social contacts that were implemented in spring 2020 to slow down infection rates of the SARS-CoV-2 virus resulted in significant modifications in mobility behaviour of urban residents. We used three-year eddy covariance measurements of size-resolved particle number fluxes from an urban site in Berlin to estimate the effects of reduced traffic intensity on particle fluxes. Similar observations of urban surface-atmosphere exchange of size-resolved particles that focus on COVID-19 lockdown-related effects are not available, yet. Although the site remained a net emission source for ultrafine particles (UFP, Dp < 100 nm), the median upward flux of ultrafine particles (FUFP) decreased from 8.78 × 107 m-2 s-1 in the reference period to 5.44 × 107 m-2 s-1 during the lockdown. This was equivalent to a relative reduction of -38 % for median FUFP, which was similar to -35 % decrease of road traffic intensity in the flux source area during that period. The size-resolved analysis demonstrated that, on average, net deposition of UFP occurred only during night when particle emission source strength by traffic was at its minimum, whereas accumulation mode particles (100 nm < Dp < 200 nm) showed net deposition also during daytime. The results indicate the benefits of traffic reductions as a mitigation strategy to reduce UFP emissions to the urban atmosphere.


Subject(s)
Air Pollutants , COVID-19 , Air Pollutants/analysis , Atmosphere , Communicable Disease Control , Environmental Monitoring/methods , Humans , Particle Size , Particulate Matter/analysis , SARS-CoV-2 , Vehicle Emissions/analysis
4.
Int J Environ Res Public Health ; 19(19)2022 Sep 30.
Article in English | MEDLINE | ID: covidwho-2065980

ABSTRACT

It remains unknown which size fractions dominate the adverse cardiopulmonary effects of particulate matter (PM). Therefore, this study aimed to explore the differential associations between size-fractioned particle number concentrations (PNCs) and cardiopulmonary function measures, including the forced expiratory volume in one second (FEV1), the forced vital capacity (FVC), and the left ventricular ejection fraction (LVEF). We conducted a panel study among 211 patients with chronic obstructive pulmonary disease (COPD) in Shanghai, China, between January 2014 and December 2021. We applied linear mixed-effect models to determine the associations between cardiopulmonary function measures and PNCs ranging from 0.01 to 10 µm in diameter. Generally, only particles <1 µm showed significant associations, i.e., ultrafine particles (UFPs, <0.1 µm) for FVC and particles ranging from 0.1 to 1 µm for FEV1 and LVEF. An interquartile range (IQR) increment in UFP was associated with decreases of 78.4 mL in FVC. PNC0.1-0.3 and PNC0.3-1 corresponded to the strongest effects on FEV1 (119.5 mL) and LVEF (1.5%) per IQR increment. Particles <1 µm might dominate the cardiopulmonary toxicity of PM, but UFPs might not always have the strongest effect. Tailored regulations towards particles <1 µm should be intensified to reduce PM pollution and protect vulnerable populations.


Subject(s)
Air Pollutants , Air Pollution , Pulmonary Disease, Chronic Obstructive , Air Pollutants/analysis , Air Pollutants/toxicity , Air Pollution/adverse effects , Air Pollution/analysis , China/epidemiology , Environmental Exposure/adverse effects , Humans , Particle Size , Particulate Matter/analysis , Stroke Volume , Ventricular Function, Left
5.
J Aerosol Med Pulm Drug Deliv ; 35(5): 239-251, 2022 10.
Article in English | MEDLINE | ID: covidwho-2062819

ABSTRACT

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, FPFrecovered of 70%, and FPFemitted 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.


Subject(s)
COVID-19 , Administration, Inhalation , Antiviral Agents , COVID-19/drug therapy , Dry Powder Inhalers , Humans , Ivermectin , Lactose , Particle Size , Powders/chemistry , Respiratory Aerosols and Droplets , SARS-CoV-2
6.
Drug Deliv ; 29(1): 3155-3167, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2062643

ABSTRACT

Resveratrol (RSV) is a phytoceutical polyphenolic compound exhibiting a well evidenced wide range of therapeutic activities. Unfortunately, its diminished aqueous solubility and extensive metabolism in gastro intestinal tract (GIT) and liver prohibit its biological activity and systemic availability. Herein the conducted study PEG stabilized emulsomes (PEMLs) were customized to enclose RSV aiming to boost its biological availability and antiviral activity. PEGylating the vesicles not only grant the promoted steric stability of the system but also being beneficial in exaggerating the intestinal permeability and extending the period of circulation of the drug, hence its targeted clinical use. The Investigation of the influence of predetermined variables on the physical characterization of formulae (entrapment efficiency EE%, particle size PS and zeta potential ZP) was implemented utilizing Design Expert® software. (F4) with desirability value (0.772), picked to be the optimal formula, which is fabricated utilizing 35 mg compritol as the lipidic core and 60 mg 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-Mpeg-2000). The dominance of the F4 relative to RSV dispersion was affirmed by the data acquired from ex-vivo and pharmacokinetic studies. In addition, F4 exhibited significant lower EC50 value (0.0127 µg/mL) relative to that of RSV dispersion(0.338 µg/mL) by around 26 times denoting the capability of the formulation to boost the antiviral activity. To a great extent, F4 was able to significantly suppress the inflammatory response and oxidative stress resulted from MERS-CoV infection on comparison with RSV dispersion. Finally, the potentiality of PEMLs as nano-panel with boosted both antiviral and oral bioavailability for RSV could be deduced based on the outcomes mentioned herein.


Subject(s)
Excipients , Polyethylene Glycols , Antiviral Agents/pharmacology , Biological Availability , Particle Size , Resveratrol
7.
Adv Drug Deliv Rev ; 189: 114527, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2060293

ABSTRACT

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.


Subject(s)
Excipients , Lactose , Administration, Inhalation , Aerosols , Chemistry, Pharmaceutical , Drug Carriers , Dry Powder Inhalers , Humans , Particle Size , Powders
8.
Mar Drugs ; 20(8)2022 Jul 25.
Article in English | MEDLINE | ID: covidwho-2023891

ABSTRACT

Nowadays, the therapeutic efficiency of small interfering RNAs (siRNA) is still limited by the efficiency of gene therapy vectors capable of carrying them inside the target cells. In this study, siRNA nanocarriers based on low molecular weight chitosan grafted with increasing proportions (5 to 55%) of diisopropylethylamine (DIPEA) groups were developed, which allowed precise control of the degree of ionization of the polycations at pH 7.4. This approach made obtaining siRNA nanocarriers with small sizes (100-200 nm), positive surface charge and enhanced colloidal stability (up to 24 h) at physiological conditions of pH (7.4) and ionic strength (150 mmol L-1) possible. Moreover, the PEGylation improved the stability of the nanoparticles, which maintained their colloidal stability and nanometric sizes even in an albumin-containing medium. The chitosan-derivatives displayed non-cytotoxic effects in both fibroblasts (NIH/3T3) and macrophages (RAW 264.7) at high N/P ratios and polymer concentrations (up to 0.5 g L-1). Confocal microscopy showed a successful uptake of nanocarriers by RAW 264.7 macrophages and a promising ability to silence green fluorescent protein (GFP) in HeLa cells. These results were confirmed by a high level of tumor necrosis factor-α (TNFα) knockdown (higher than 60%) in LPS-stimulated macrophages treated with the siRNA-loaded nanoparticles even in the FBS-containing medium, findings that reveal a good correlation between the degree of ionization of the polycations and the physicochemical properties of nanocarriers. Overall, this study provides an approach to enhance siRNA condensation by chitosan-based carriers and highlights the potential of these nanocarriers for in vivo studies.


Subject(s)
Chitosan , Nanoparticles , Chitosan/chemistry , HeLa Cells , Humans , Nanoparticles/chemistry , Particle Size , Polyethylene Glycols/chemistry , RNA, Small Interfering/metabolism
9.
Int J Environ Res Public Health ; 19(17)2022 Aug 30.
Article in English | MEDLINE | ID: covidwho-2023706

ABSTRACT

This study uses behavioral observation, interviews, and questionnaire research to investigate the residential environment. It also evaluates the elderly in four representative ancient towns of Xiangxi, namely, Liye Ancient Town, Furong Ancient Town, Liexi Ancient Town, and Xichehe Ancient Town. It includes indoor air (CO2, PM2.5, PM10) and light intensity monitoring for the residential environment. The results showed that the elderly had a significant sense of frustration and loneliness. Of the elderyly, 70% believed the current living environment had an impact on healthy living, and 45% believed the safety and convenience of the living environment should be improved. More than 80% of the elderly were dissatisfied with their indoor acoustic environment, and more than 70% were dissatisfied with their home transportation. More than 85% of the elderly considered traditional wooden components and spaces to be the source of cultural identity. Furthermore, the average indoor PM2.5 concentration during the fire pit fire was 350-600 µg/m3, about 4.7-8 times the Chinese standard value. The average concentration of PM10 in all rooms was more than 400 µg/m3, approximately three times the Chinese standard value. Also, targeted environmental improvement strategies were proposed. The study results provided actual information to develop a systematic approach and a targeted design based on the needs to improve the residential environment of the elderly in ancient cities.


Subject(s)
Air Pollutants , Air Pollution, Indoor , Aged , Air Pollutants/analysis , Air Pollution, Indoor/analysis , Cities , Environmental Monitoring/methods , Humans , Particle Size , Particulate Matter/analysis , Surveys and Questionnaires
10.
Drug Deliv ; 29(1): 2868-2882, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-2008413

ABSTRACT

Loratadine (LORA), is a topical antihistamine utilized in the treatment of ocular symptoms of COVID-19. The study aimed to develop a Loratadine Nanostructured Lipid Carriers Ocugel (LORA-NLCs Ocugel), enhance its solubility, trans-corneal penetrability, and bioavailability. full-factorial design was established with 24 trials to investigate the impact of several variables upon NLCs properties. LORA-NLCs were fabricated by using hot melt emulsification combined with high-speed stirring and ultrasonication methods. All obtained formulae were assessed in terms of percent of entrapment efficiency (EE%), size of the particle (PS), zeta potential (ZP), as well as in-vitro release. Via using Design Expert® software the optimum formula was selected, characterized using FTIR, Raman spectroscopy, and stability studies. Gel-based of optimized LORA-NLCs was prepared using 4% HPMC k100m which was further evaluated in terms of physicochemical properties, Ex-vivo, and In-vivo studies. The optimized LORA-NLCs, comprising Compritol 888 ATO®, Labrasol®, and Span® 60 showed EE% of 95.78 ± 0.67%, PS of 156.11 ± 0.54 nm, ZP of -40.10 ± 0.55 Mv, and Qh6% of 99.67 ± 1.09%, respectively. Additionally, it illustrated a spherical morphology and compatibility of LORA with other excipients. Consequently, gel-based on optimized LORA-NLCs showed pH (7.11 ± 0.52), drug content (98.62%± 1.31%), viscosity 2736 cp, and Q12% (90.49 ± 1.32%). LORA-NLCs and LORA-NLCs Ocugel exhibited higher ex-vivo trans-corneal penetrability compared with the aqueous drug dispersion. Confocal laser scanning showed valuable penetration of fluoro-labeled optimized formula and LORA-NLCs Ocugel through corneal. The optimized formula was subjected to an ocular irritation test (Draize Test) that showed the absence of any signs of inflammation in rabbits, and histological analysis showed no effect or damage to rabbit eyeballs. Cmax and the AUC0-24 were higher in LORA-NLCs Ocugel compared with pure Lora dispersion-loaded gel The research findings confirmed that NLCs could enhance solubility, trans-corneal penetrability, and the bioavailability of LORA.


Subject(s)
COVID-19 , Loratadine , Animals , COVID-19/drug therapy , Drug Carriers/chemistry , Lipids/chemistry , Particle Size , Rabbits
11.
Comput Methods Programs Biomed ; 225: 107094, 2022 Oct.
Article in English | MEDLINE | ID: covidwho-2007619

ABSTRACT

BACKGROUND AND OBJECTIVE: Pulmonary fibrosis (PF) is a chronic progressive disease with an extremely high mortality rate and is a complication of COVID-19. Inhalable microspheres have been increasingly used in the treatment of lung diseases such as PF in recent years. Compared to the direct inhalation of drugs, a larger particle size is required to ensure the sustained release of microspheres. However, the clinical symptoms of PF may lead to the easier deposition of microspheres in the upper respiratory tract. Therefore, it is necessary to understand the effects of PF on the deposition of microspheres in the respiratory tract. METHODS: In this study, airway models with different degrees of PF in humans and mice were established, and the transport and deposition of microspheres in the airway were simulated using computational fluid dynamics. RESULTS: The simulation results showed that PF increases microsphere deposition in the upper respiratory tract and decreases bronchial deposition in both humans and mice. Porous microspheres with low density can ensure deposition in the lower respiratory tract and larger particle size. In healthy and PF humans, porous microspheres of 10 µm with densities of 700 and 400 kg/m³ were deposited most in the bronchi. Unlike in humans, microspheres larger than 4 µm are completely deposited in the upper respiratory tract of mice owing to their high inhalation velocity. For healthy and PF mice, microspheres of 6 µm with densities of and 100 kg/m³ are recommended. CONCLUSIONS: The results showed that with the exacerbation of PF, it is more difficult for microsphere particles to deposit in the subsequent airway. In addition, there were significant differences in the deposition patterns among the different species. Therefore, it is necessary to process specific microspheres from different individuals. Our study can guide the processing of microspheres and achieve differentiated drug delivery in different subjects to maximize therapeutic effects.


Subject(s)
COVID-19 , Pulmonary Fibrosis , Animals , Computer Simulation , Delayed-Action Preparations , Humans , Lung , Mice , Microspheres , Models, Biological , Particle Size , Porosity , Pulmonary Fibrosis/drug therapy , Respiratory Aerosols and Droplets , Trachea
12.
Food Chem ; 396: 133639, 2022 Dec 01.
Article in English | MEDLINE | ID: covidwho-1996165

ABSTRACT

The resistance of microorganisms against commonly used antibiotics is becoming an increasingly important problem in the food and pharmaceutical industries. Therefore, the development of novel bactericidal agents, as well as the design of drug delivery systems based on materials composed of biocompatible and biodegradable building blocks, has attracted increasing attention. To address this challenge, microparticles composed of l-lactide homopolymer and l-lactide/1,3-dioxolane (co)polymers loaded with quercetin (Q) were fabricated by using a microfluidic technique. This method enables the preparation of homogeneous particles with sizes ranging from 60 to 80 µm, composed of degradable semicrystalline or amorphous (co)polyesters. The microencapsulation of Q in a (co)polymeric matrix enables prolonged release of the antimicrobial agent. The antibacterial properties of the obtained biocompatible microparticles are confirmed by the agar diffusion plate method for various bacterial strains. Therefore, Q-loaded microparticles can have important applications in food preservation as a novel antimicrobial system.


Subject(s)
Lactic Acid , Polyglycolic Acid , Anti-Bacterial Agents/pharmacology , Delayed-Action Preparations/chemistry , Dioxanes , Dioxolanes , Lactic Acid/chemistry , Microfluidics , Particle Size , Polyesters/chemistry , Polyglycolic Acid/chemistry , Polylactic Acid-Polyglycolic Acid Copolymer , Quercetin
13.
J Hazard Mater ; 422: 126783, 2022 01 15.
Article in English | MEDLINE | ID: covidwho-1347177

ABSTRACT

We designed a novel experimental set-up to pseudo-simultaneously measure size-segregated filtration efficiency (ηF), breathing resistance (ηP) and potential usage time (tB) for 11 types of face protective equipment (FPE; four respirators; three medical; and four handmade) in the submicron range. As expected, the highest ηF was exhibited by respirators (97 ± 3%), followed by medical (81 ± 7%) and handmade (47 ± 13%). Similarly, the breathing resistance was highest for respirators, followed by medical and handmade FPE. Combined analysis of efficiency and breathing resistance highlighted trade-offs, i.e. respirators showing the best overall performance across these two indicators, followed by medical and handmade FPE. This hierarchy was also confirmed by quality factor, which is a performance indicator of filters. Detailed assessment of size-segregated aerosols, combined with the scanning electron microscope imaging, revealed material characteristics such as pore density, fiber thickness, filter material and number of layers influence their performance. ηF and ηP showed an inverse exponential decay with time. Using their cross-over point, in combination with acceptable breathability, allowed to estimate tB as 3.2-9.5 h (respirators), 2.6-7.3 h (medical masks) and 4.0-8.8 h (handmade). While relatively longer tB of handmade FPE indicate breathing comfort, they are far less efficient in filtering virus-laden submicron aerosols compared with respirators.


Subject(s)
Masks , Respiratory Protective Devices , Aerosols , Filtration , Particle Size
14.
Environ Res ; 211: 113055, 2022 08.
Article in English | MEDLINE | ID: covidwho-1972077

ABSTRACT

To better understand the change characteristics and reduction in organic carbon (OC) and elemental carbon (EC) in particulate matter (PM) with a diameter of ≤2.5 µm (PM2.5) driven by the most stringent clean air policies and pandemic-related lockdown measures in China, a comprehensive field campaign was performed to measure the carbonaceous components in PM2.5 on an hourly basis via harmonized analytical methods in the Beijing-Tianjin-Hebei and its surrounding region (including 2 + 26 cities) from January 1 to December 31, 2020. The results indicated that the annual average concentrations of OC and EC reached as low as 6.6 ± 5.7 and 1.8 ± 1.9 µg/m3, respectively, lower than those obtained in previous studies, which could be attributed to the effectiveness of the Clean Air Action Plan and the impact of the COVID-19-related lockdown measures implemented in China. Marked seasonal and diurnal variations in OC and EC were observed in the 2 + 26 cities. Significant correlations (p < 0.001) between OC and EC were found. The annual average secondary OC levels level ranged from 1.8-5.4 µg/m3, accounting for 37.7-73.0% of the OC concentration in the 2 + 26 cities estimated with the minimum R squared method. Based on Interagency Monitoring of Protected Visual Environments (IMPROVE) algorithms, the light extinction contribution of carbonaceous PM to the total amount reached 21.1% and 26.0% on average, suggesting that carbonaceous PM played a less important role in visibility impairment than did the other chemical components in PM2.5. This study is expected to provide an important real-time dataset and in-depth analysis of the significant reduction in OC and EC in PM2.5 driven by both the Clean Air Action Plan and COVID-19-related lockdown policies over the past few years, which could represent an insightful comparative case study for other developing countries/regions facing similar carbonaceous PM pollution.


Subject(s)
Air Pollutants , COVID-19 , Aerosols/analysis , Air Pollutants/analysis , COVID-19/prevention & control , Carbon/analysis , China , Cities , Communicable Disease Control , Environmental Monitoring , Humans , Particle Size , Particulate Matter/analysis , Seasons
15.
Mar Drugs ; 19(2)2021 Jan 27.
Article in English | MEDLINE | ID: covidwho-1969360

ABSTRACT

Inorganic polyphosphate (polyP) is a widely distributed polymer found from bacteria to animals, including marine species. This polymer exhibits morphogenetic as well as antiviral activity and releases metabolic energy after enzymatic hydrolysis also in human cells. In the pathogenesis of the coronavirus disease 2019 (COVID-19), the platelets are at the frontline of this syndrome. Platelets release a set of molecules, among them polyP. In addition, the production of airway mucus, the first line of body defense, is impaired in those patients. Therefore, in this study, amorphous nanoparticles of the magnesium salt of polyP (Mg-polyP-NP), matching the size of the coronavirus SARS-CoV-2, were prepared and loaded with the secondary plant metabolite quercetin or with dexamethasone to study their effects on the respiratory epithelium using human alveolar basal epithelial A549 cells as a model. The results revealed that both compounds embedded into the polyP nanoparticles significantly increased the steady-state-expression of the MUC5AC gene. This mucin species is the major mucus glycoprotein present in the secreted gel-forming mucus. The level of gene expression caused by quercetin or with dexamethasone, if caged into polyP NP, is significantly higher compared to the individual drugs alone. Both quercetin and dexamethasone did not impair the growth-supporting effect of polyP on A549 cells even at concentrations of quercetin which are cytotoxic for the cells. A possible mechanism of the effects of the two drugs together with polyP on mucin expression is proposed based on the scavenging of free oxygen species and the generation of ADP/ATP from the polyP, which is needed for the organization of the protective mucin-based mucus layer.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Dexamethasone/pharmacology , Mucin 5AC/biosynthesis , Mucin 5AC/drug effects , Quercetin/pharmacology , A549 Cells , Anti-Inflammatory Agents/chemistry , Antioxidants/chemistry , COVID-19 , Dexamethasone/chemistry , Free Radical Scavengers/pharmacology , Gene Expression Regulation/drug effects , Humans , Magnesium/chemistry , Mucin 5AC/genetics , Mucins/biosynthesis , Mucins/chemistry , Nanoparticles , Particle Size , Plants/chemistry , Polyphosphates/chemistry , Quercetin/chemistry , Reactive Oxygen Species
16.
J Nanobiotechnology ; 20(1): 272, 2022 Jun 11.
Article in English | MEDLINE | ID: covidwho-1940509

ABSTRACT

BACKGROUND: Acute lung injury (ALI), a severe health-threatening disease, has a risk of causing chronic pulmonary fibrosis. Informative and powerful evidence suggests that inflammation and oxidative stress play a central role in the pathogenesis of ALI. Quercetin is well recognized for its excellent antioxidant and anti-inflammatory properties, which showed great potential for ALI treatment. However, the application of quercetin is often hindered by its low solubility and bioavailability. Therefore, to overcome these challenges, an inhalable quercetin-alginate nanogel (QU-Nanogel) was fabricated, and by this special "material-drug" structure, the solubility and bioavailability of quercetin were significantly enhanced, which could further increase the activity of quercetin and provide a promising therapy for ALI. RESULTS: QU-Nanogel is a novel alginate and quercetin based "material-drug" structural inhalable nanogel, in which quercetin was stabilized by hydrogen bonding to obtain a "co-construct" water-soluble nanogel system, showing antioxidant and anti-inflammatory properties. QU-Nanogel has an even distribution in size of less than 100 nm and good biocompatibility, which shows a stronger protective and antioxidant effect in vitro. Tissue distribution results provided evidence that the QU-Nanogel by ultrasonic aerosol inhalation is a feasible approach to targeted pulmonary drug delivery. Moreover, QU-Nanogel was remarkably reversed ALI rats by relieving oxidative stress damage and acting the down-regulation effects of mRNA and protein expression of inflammation cytokines via ultrasonic aerosol inhalation administration. CONCLUSIONS: In the ALI rat model, this novel nanogel showed an excellent therapeutic effect by ultrasonic aerosol inhalation administration by protecting and reducing pulmonary inflammation, thereby preventing subsequent pulmonary fibrosis. This work demonstrates that this inhalable QU-Nanogel may function as a promising drug delivery strategy in treating ALI.


Subject(s)
Acute Lung Injury , Pulmonary Fibrosis , Acute Lung Injury/drug therapy , Alginates , Animals , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Antioxidants/chemistry , Inflammation , Nanogels , Particle Size , Quercetin/pharmacology , Quercetin/therapeutic use , Rats
17.
J Hazard Mater ; 439: 129669, 2022 10 05.
Article in English | MEDLINE | ID: covidwho-1956210

ABSTRACT

Fly ash is a common solid residue of incineration plants and poses a great environmental concern because of its toxicity upon inhalation exposure. The inhalation health impacts of fly ash is closely related to its transport and deposition in the human respiratory system which warrants significant research for health guideline setting and inhalation exposure protection. In this study, a series of fly ash transport and deposition experiments have been carried out in a bifurcation airway model by optical aerosol sampling analysis. Three types of fly ash samples of different morphologies were tested and their respiratory deposition and transport processes were compared. The deposition efficiencies were calculated and relevant transport dynamics mechanisms were discussed. The influences of physiological conditions such as breathing rate, duration, and fly ash physical properties (size, morphology, and specific surface area) were investigated. The deposition characteristics of respiratory particles containing SARS-CoV-2 has also been analyzed, which could further provide some guidance on COVID-19 prevention. The results could potentially serve as a basis for setting health guidelines and recommending personal respiratory protective equipment for fly ash handlers and people who are in the high exposure risk environment for COVID-19 transmission.


Subject(s)
COVID-19 , Coal Ash , Coal Ash/chemistry , Humans , Incineration , Particle Size , Particulate Matter/analysis , Particulate Matter/toxicity , Respiratory System , SARS-CoV-2
18.
Chemosphere ; 307(Pt 1): 135708, 2022 Nov.
Article in English | MEDLINE | ID: covidwho-1936146

ABSTRACT

The coronavirus (COVID-19) is becoming more threatening with the emergence of new mutations. New virus transmission and infection processes remain challenging and re-examinations of proper protection methods are urgently needed. From fluid dynamic viewpoint, the transmission of virus-carrying droplets and aerosols is one key to understanding the virus-transmission mechanisms. This study shows virus transmission by incorporating flow-evaporation model into the Navier-Stokes equation to describe the group of airborne sputum droplets exhaled under Rosin-Rammler distribution. Solid components and humidity field evolution are incorporated in describing droplet and ambient conditions. The numerical model is solved by an inhouse code using advection-diffusion equation for the temperature field and the humidity field, discretized by applying the total-variation diminishing Runge-Kutta method. The results of this study are presented in detail to show the different trends under various ambient conditions and to reveal the major viral-transmission routes as a function of droplet size.


Subject(s)
COVID-19 , Humans , Humidity , Particle Size , Respiratory Aerosols and Droplets , Sputum
19.
J Aerosol Med Pulm Drug Deliv ; 35(3): 121-138, 2022 06.
Article in English | MEDLINE | ID: covidwho-1927267

ABSTRACT

Vaccines are a very important tool in the effort to reduce the global burden of infectious diseases. Modern vaccines can be formulated in several ways to induce specific immunity, including through the use of live bacteria, subunit antigens, and even genetic material. However, vaccines typically need to be transported and stored under controlled refrigerated or frozen conditions to maintain potency. This strict temperature control is incompatible with the available infrastructure in many developing countries. One method of improving the thermostability of a vaccine is through drying of a liquid presentation into a dry dosage form. In addition to enhancing the capability for distribution in resource-poor settings, these dry vaccine forms are more suitable for long-term stockpiling. Spray drying is a drying method that has been successfully used to stabilize many experimental vaccines into a dry form for storage above refrigerated temperatures. Additionally, the use of spray drying allows for the production of engineered particles suitable for respiratory administration. These particles can be further designed for increased out-of-package robustness against high humidity. Furthermore, there are already commercial dry powder delivery devices available that can be used to safely deliver vaccines to the respiratory system. The research in this field demonstrates that the resources to develop highly stable vaccines in flexible dosage forms are available and that these presentations offer many advantages for global vaccination campaigns.


Subject(s)
Spray Drying , Vaccines , Administration, Inhalation , Drug Compounding , Particle Size , Powders/chemistry , Vaccines/chemistry
20.
Pharm Dev Technol ; 27(6): 635-645, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1915404

ABSTRACT

Remdesivir is one of the effective drugs proposed for the treatment of coronavirus disease 2019 (COVID-19). However, the study on inhalable regimen is currently limited though COVID-19 is respiratory diseases and infects lung area. This work aims to prepare inhalable remdesivir formulations and verify their effectiveness through in vitro evaluations. Formulations containing different ratios of jet-milled inhalable remdesivir (5, 10, 20,40, and 70%) with excipients were produced and characterized in terms of the particle size distribution, particle morphology, flowability, water content, crystallinity, the water sorption and desorption capabilities, and the aerodynamic performance. Results indicating that drug loading are a vital factor in facilitating the dispersion of remdesivir dry powder, and the ternary excipient plays a negligible role in improving aerosol performance. Besides, the 70% remdesivir with lactose carrier (70% RD-Lac) was physically stable and retain high aerosol performance after conditioned at 40 °C and 75% RH for a month. Therefore, formulation 70% RD-Lac might be recommended as a candidate product for the potential treatment of COVID-19.


Subject(s)
COVID-19 , Excipients , Adenosine Monophosphate/analogs & derivatives , Administration, Inhalation , Alanine/analogs & derivatives , COVID-19/drug therapy , Dry Powder Inhalers/methods , Humans , Lactose , Particle Size , Powders , Respiratory Aerosols and Droplets , Water
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