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2.
Molecules ; 28(11)2023 May 30.
Article in English | MEDLINE | ID: covidwho-20238682

ABSTRACT

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.


Subject(s)
Acute Lung Injury , Benzylisoquinolines , COVID-19 , Rats , Animals , Administration, Inhalation , Dry Powder Inhalers , COVID-19/metabolism , SARS-CoV-2 , Respiratory Aerosols and Droplets , Lung/metabolism , Acute Lung Injury/drug therapy , Acute Lung Injury/metabolism , Benzylisoquinolines/pharmacology , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Anti-Inflammatory Agents/analysis , Particle Size , Powders/analysis
4.
Proc Natl Acad Sci U S A ; 120(22): e2301145120, 2023 05 30.
Article in English | MEDLINE | ID: covidwho-2326129

ABSTRACT

Airborne respiratory aerosol particle transmission of pathogens such as severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), influenza, or rhinoviruses plays a major role in the spread of infectious diseases. The infection risk is increased during indoor exercise, as aerosol particle emission can increase by more than 100-fold from rest to maximal exercise. Earlier studies have investigated the effect of factors such as age, sex, and body mass index (BMI), but only at rest and without taking ventilation into account. Here, we report that during both rest and exercise, subjects aged 60 to 76 y emit on average more than twice as many aerosol particles per minute than subjects aged 20 to 39 y. In terms of volume, older subjects emit on average five times as much dry volume (i.e., the residue of dried aerosol particles) than younger subjects. There was no statistically significant effect of sex or BMI within the test group. Together, this suggests that aging of the lung and respiratory tract is associated with an increased generation of aerosol particles irrespective of ventilation. Our findings demonstrate that age and exercise increase aerosol particle emission. In contrast, sex or BMI only have minor effects.


Subject(s)
COVID-19 , SARS-CoV-2 , Humans , Particle Size , Respiratory Aerosols and Droplets , Lung
5.
Int J Pharm ; 640: 122983, 2023 Jun 10.
Article in English | MEDLINE | ID: covidwho-2320484

ABSTRACT

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.


Subject(s)
COVID-19 , Chemistry, Pharmaceutical , Humans , Chemistry, Pharmaceutical/methods , Administration, Inhalation , COVID-19 Drug Treatment , Lung , Particle Size , Powders/chemistry , Dry Powder Inhalers
6.
Int J Mol Sci ; 24(9)2023 Apr 27.
Article in English | MEDLINE | ID: covidwho-2319074

ABSTRACT

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.


Subject(s)
Copper , Particle Size , Powders
7.
Biosens Bioelectron ; 234: 115356, 2023 Aug 15.
Article in English | MEDLINE | ID: covidwho-2310195

ABSTRACT

The COVID-19 pandemic ignited massive research into the rapid detection of bioaerosols. In particular, nanotechnology-based detection strategies are proposed as alternatives because of issues in bioaerosol enrichment and lead time for molecular diagnostics; however, the practical implementation of such techniques is still unclear due to obstacles regarding the large research and development effort and investment for the validation. The use of adenosine triphosphate (ATP) bioluminescence (expressed as relative luminescence unit (RLU) per unit volume of air) of airborne particulate matter (PM) to determine the bacterial population as a representative of the total bioaerosols (viruses, bacteria, and fungi) has been raised frequently because of the high reponse speed, resolution, and compatibility with culture-based bioaerosol monitoring. On the other hand, additional engineering attempts are required to confer significance because of the size-classified (bioluminescence for different PM sizes) and specific (bioluminescence per unit PM mass) biological risks of air for providing proper interventions in the case of airborne transmission. In this study, disc-type impactors to cut-off aerosols larger than 1 µm, 2.5 µm, and 10 µm were designed and constructed to collect PM1, PM2.5, and PM10 on sampling swabs. This engineering enabled reliable size-classified bioluminescence signals using a commercial ATP luminometer after just 5 min of air intake. The simultaneous operations of a six-stage Andersen impactor and optical PM spectrometers were conducted to determine the correlations between the resulting RLU and colony forming unit (CFU; from the Andersen impactor) or PM mass concentration (deriving specific bioluminescence).


Subject(s)
Biosensing Techniques , COVID-19 , Humans , Adenosine Triphosphate/analysis , Pandemics , Air Microbiology , Biosensing Techniques/methods , COVID-19/diagnosis , Respiratory Aerosols and Droplets , Bacteria , Fungi , Environmental Monitoring/methods , Particle Size
8.
Environ Res ; 231(Pt 1): 116068, 2023 Aug 15.
Article in English | MEDLINE | ID: covidwho-2309520

ABSTRACT

Urban air fine particles are a major health-relating problem. However, it is not well understood how the health-relevant features of fine particles should be monitored. Limitations of PM2.5 (mass concentration of sub 2.5 µm particles), which is commonly used in the health effect estimations, have been recognized and, e.g., World Health Organization (WHO) has released good practice statements for particle number (PN) and black carbon (BC) concentrations (2021). In this study, a characterization of urban wintertime aerosol was done in three environments: a detached housing area with residential wood combustion, traffic-influenced streets in a city centre and near an airport. The particle characteristics varied significantly between the locations, resulting different average particle sizes causing lung deposited surface area (LDSA). Near the airport, departing planes had a major contribution on PN, and most particles were smaller than 10 nm, similarly as in the city centre. The high hourly mean PN (>20 000 1/cm3) stated in the WHO's good practices was clearly exceeded near the airport and in the city centre, even though traffic rates were reduced due to a SARS-CoV-2-related partial lockdown. In the residential area, wood combustion increased both BC and PM2.5, but also PN of sub 10 and 23 nm particles. The high concentrations of sub 10 nm particles in all the locations show the importance of the chosen lower size limit of PN measurement, e.g., WHO states that the lower limit should be 10 nm or smaller. Furthermore, due to ultrafine particle emissions, LDSA per unit PM2.5 was 1.4 and 2.4 times higher near the airport than in the city centre and the residential area, respectively, indicating that health effects of PM2.5 depend on urban environment as well as conditions, and emphasizing the importance of PN monitoring in terms of health effects related to local pollution sources.


Subject(s)
Air Pollutants , Air Pollution , COVID-19 , Humans , Particulate Matter/analysis , Air Pollutants/analysis , Environmental Monitoring/methods , SARS-CoV-2 , Communicable Disease Control , Respiratory Aerosols and Droplets , Air Pollution/analysis , Particle Size , Lung/chemistry , Soot , Vehicle Emissions/analysis
9.
Environ Sci Pollut Res Int ; 30(12): 33206-33228, 2023 Mar.
Article in English | MEDLINE | ID: covidwho-2289596

ABSTRACT

This paper presents the numerical results of particle propagation in open space, taking into account the temperature of the human body and the surface of the ground. And also, the settling of particles or droplets under the action of gravitational force and transport in the open air is taken into account, taking into account the temperature during the process of breathing and sneezing or coughing. The temperature of the body and the surface of the ground, different rates of particle emission from the mouth, such as breathing and coughing or sneezing, are numerically investigated. The effect of temperature, cross-inlet wind, and the velocity of particle ejection from a person's mouth on social distancing is being investigated using a numerical calculation. The variable temperature of the human body forms a thermal plume, which affects the increase in the trajectory of the particle propagation, taking into account the lateral air flow. The thermal plume affects the particles in the breathing zone and spreads the particles over long distances in the direction of the airflow. The result of this work shows that in open space, taking into account the temperature of the body and the surface of the ground, a 2-m social distance may be insufficient for the process of sneezing and social distance must be observed depending on the breathing mode.


Subject(s)
Human Body , Wind , Humans , Temperature , Particle Size , Physical Distancing , Respiratory Aerosols and Droplets , Sneezing
10.
J Control Release ; 358: 128-141, 2023 06.
Article in English | MEDLINE | ID: covidwho-2303394

ABSTRACT

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.


Subject(s)
Antibodies, Monoclonal , COVID-19 , Humans , Powders , SARS-CoV-2 , Respiratory Aerosols and Droplets , Administration, Inhalation , Particle Size , Dry Powder Inhalers
11.
Eur J Pharm Biopharm ; 187: 141-155, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-2306002

ABSTRACT

Clofazimine, an anti-leprosy drug, has been anticipated for a candidate to treat tuberculosis, cryptosporidiosis, and coronavirus infection, but its low oral bioavailability is considered a reason for its limited activity. In the current study, we have tried to improve the oral bioavailability of clofazimine by several SNEDDS formulations and characterized the absorption behavior from various aspects. Among four SNEDDS formulations prepared, SNEDDS A, prepared with castor oil as an oil component, provided the highest bioavailability (around 61%) and SNEDDS D, prepared with Capryol 90, gave the second highest bioavailability. SNEDDS A formed the finest nanoparticles, which were maintained under gastric and intestinal luminal conditions. The comparison in oral bioavailability between the SNEDDS formulation and its corresponding preformed nanoemulsion suggested that SNEDDS A would efficiently form nanoemulsion in the gastrointestinal tract after oral administration. AUC of mesenteric lymph node concentration was the highest for SNEDDS A, which would be one of the reasons for SNEDDS A to reveal the highest oral bioavailability. A cycloheximide-treated oral absorption study and single-pass perfusion study by utilizing a vascular-luminal perfused small intestine-liver preparation clearly indicated that over 90% of clofazimine absorbed to systemic circulation should be derived from lymphatic transport for both SNEDDS A and D. Furthermore, the fraction of dose absorbed was around 65% for SNEDDS D, but SNEDDS A achieved around 94%, indicating the excellent performance of SNEDDS A.


Subject(s)
Clofazimine , Nanoparticles , Drug Delivery Systems , Solubility , Pharmaceutical Preparations , Administration, Oral , Biological Availability , Nanoparticles/chemistry , Emulsions/chemistry , Particle Size
12.
Sci Total Environ ; 874: 162540, 2023 May 20.
Article in English | MEDLINE | ID: covidwho-2275809

ABSTRACT

Auckland is a city with limited industrial activity, road traffic being the dominant source of air pollution. Thus, the time periods when social contact and movement in Auckland were severely curtailed due to COVID-19 restrictions presented a unique opportunity to observe impacts on pedestrian exposure to air pollution under a range of different traffic flow scenarios, providing insights into the impacts of potential future traffic calming measures. Pedestrian exposure to ultrafine particles (UFPs), was measured using personal monitoring along a customised route through Central Auckland during different COVID-19-affected traffic flow conditions. Results showed that reduced traffic flows led to statistically significant reductions in average exposure to UFP under all traffic reduction scenarios (TRS). However, the size of the reduction was variable in both time and place. Under the most stringent TRS (traffic reduction of 82 %), median ultrafine particle (UFP) concentrations reduced by 73 %. Under the less stringent scenario, the extent of reduction varied in time and space; a traffic reduction of 62 % resulted in a 23 % reduction in median UFP concentrations in 2020 but in 2021 similar traffic reductions led to a decrease in median UFP concentrations of 71 %. Under all scenarios, the magnitude of the impact of traffic reductions on UFP exposure varied along the route, with areas dominated by emissions from construction and ferry/port activities showing little correlation between traffic flow and exposure. Shared traffic spaces, previously pedestrianised, also recorded consistently high concentrations with little variability observed. This study provided a unique opportunity to assess the potential benefits and risks of such zones and to help decision-makers evaluate future traffic management interventions (such as low emissions zones). The results suggest that controlled traffic flow interventions can result in a significant reduction in pedestrian exposure to UFPs, but that the magnitude of reductions is sensitive to local-scale variations in meteorology, urban land use and traffic flow patterns.


Subject(s)
Air Pollutants , Air Pollution , COVID-19 , Humans , Particulate Matter/analysis , Air Pollutants/analysis , Vehicle Emissions/analysis , Environmental Monitoring/methods , Air Pollution/analysis , Particle Size
13.
Int J Environ Res Public Health ; 20(5)2023 03 04.
Article in English | MEDLINE | ID: covidwho-2275180

ABSTRACT

The health effects of particles are directly related to their deposition patterns (deposition site and amount) in human airways. However, estimating the particle trajectory in a large-scale human lung airway model is still a challenge. In this work, a truncated single-path, large-scale human airway model (G3-G10) with a stochastically coupled boundary method were employed to investigate the particle trajectory and the roles of their deposition mechanisms. The deposition patterns of particles with diameters (dp) of 1-10 µm are investigated under various inlet Reynolds numbers (Re = 100-2000). Inertial impaction, gravitational sedimentation, and combined mechanism were considered. With the increasing airway generations, the deposition of smaller particles (dp < 4 µm) increased due to gravitational sedimentation, while that of larger particles decreased due to inertial impaction. The obtained formulas of Stokes number and Re can predict the deposition efficiency due to the combined mechanism in the present model, and the prediction can be used to assess the dose-effect of atmospheric aerosols on the human body. Diseases in deeper generations are mainly attributed to the deposition of smaller particles under lower inhalation rates, while diseases at the proximal generations mainly result from the deposition of larger particles under higher inhalation rates.


Subject(s)
Lung , Models, Biological , Humans , Particle Size , Computer Simulation , Aerosols , Administration, Inhalation
14.
Molecules ; 28(5)2023 Feb 28.
Article in English | MEDLINE | ID: covidwho-2265862

ABSTRACT

Oral anticancer therapy mostly faces the challenges of low aqueous solubility, poor and irregular absorption from the gastrointestinal tract, food-influenced absorption, high first-pass metabolism, non-targeted delivery, and severe systemic and local adverse effects. Interest has been growing in bioactive self-nanoemulsifying drug delivery systems (bio-SNEDDSs) using lipid-based excipients within nanomedicine. This study aimed to develop novel bio-SNEDDS to deliver antiviral remdesivir and baricitinib for the treatment of breast and lung cancers. Pure natural oils used in bio-SNEDDS were analyzed using GC-MS to examine bioactive constituents. The initial evaluation of bio-SNEDDSs were performed based on self-emulsification assessment, particle size analysis, zeta potential, viscosity measurement, and transmission electron microscopy (TEM). The single and combined anticancer effects of remdesivir and baricitinib in different bio-SNEDDS formulations were investigated in MDA-MB-231 (breast cancer) and A549 (lung cancer) cell lines. The results from the GC-MS analysis of bioactive oils BSO and FSO showed pharmacologically active constituents, such as thymoquinone, isoborneol, paeonol and p-cymenene, and squalene, respectively. The representative F5 bio-SNEDDSs showed relatively uniform, nanosized (247 nm) droplet along with acceptable zeta potential values (+29 mV). The viscosity of the F5 bio-SNEDDS was recorded within 0.69 Cp. The TEM suggested uniform spherical droplets upon aqueous dispersions. Drug-free, remdesivir and baricitinib-loaded bio-SNEDDSs (combined) showed superior anticancer effects with IC50 value that ranged from 1.9-4.2 µg/mL (for breast cancer), 2.4-5.8 µg/mL (for lung cancer), and 3.05-5.44 µg/mL (human fibroblasts cell line). In conclusion, the representative F5 bio-SNEDDS could be a promising candidate for improving the anticancer effect of remdesivir and baricitinib along with their existing antiviral performance in combined dosage form.


Subject(s)
Breast Neoplasms , Lung Neoplasms , Nanoparticles , Humans , Female , Drug Repositioning , Administration, Oral , Emulsions , Drug Delivery Systems/methods , Solubility , Oils , Particle Size , Biological Availability , Surface-Active Agents , Drug Liberation
15.
AAPS PharmSciTech ; 24(4): 98, 2023 Apr 04.
Article in English | MEDLINE | ID: covidwho-2254236

ABSTRACT

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.


Subject(s)
COVID-19 , Nanoparticles , Humans , Powders , Administration, Inhalation , Drug Delivery Systems/methods , Translational Research, Biomedical , COVID-19 Vaccines , Respiratory Aerosols and Droplets , Dry Powder Inhalers , Particle Size
16.
J Pharm Sci ; 112(5): 1341-1344, 2023 05.
Article in English | MEDLINE | ID: covidwho-2241643

ABSTRACT

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.


Subject(s)
Biological Products , COVID-19 , Humans , Protein Aggregates , Pandemics , Administration, Inhalation , Powders , Particle Size , Dry Powder Inhalers , Respiratory Aerosols and Droplets
17.
Molecules ; 28(4)2023 Feb 15.
Article in English | MEDLINE | ID: covidwho-2238498

ABSTRACT

The oral delivery system is very important and plays a significant role in increasing the solubility of drugs, which eventually will increase their absorption by the digestive system and enhance the drug bioactivity. This study was conducted to synthesize a novel curcumin nano lipid carrier (NLC) and use it as a drug carrier with the help of computational molecular docking to investigate its solubility in different solid and liquid lipids to choose the optimum lipids candidate for the NLCs formulation and avoid the ordinary methods that consume more time, materials, cost, and efforts during laboratory experiments. The antiviral activity of the formed curcumin-NLC against SARS-CoV-2 (COVID-19) was assessed through a molecular docking study of curcumin's affinity towards the host cell receptors. The novel curcumin drug carrier was synthesized as NLC using a hot and high-pressure homogenization method. Twenty different compositions of the drug carrier (curcumin nano lipid) were synthesized and characterized using different physicochemical techniques such as UV-Vis, FTIR, DSC, XRD, particle size, the zeta potential, and AFM. The in vitro and ex vivo studies were also conducted to test the solubility and the permeability of the 20 curcumin-NLC formulations. The NLC as a drug carrier shows an enormous enhancement in the solubility and permeability of the drug.


Subject(s)
COVID-19 , Curcumin , Nanostructures , Humans , Curcumin/chemistry , Lipids/chemistry , Molecular Docking Simulation , SARS-CoV-2 , Drug Carriers/chemistry , Particle Size , Nanostructures/chemistry
18.
J Microencapsul ; 40(4): 217-232, 2023 Jun.
Article in English | MEDLINE | ID: covidwho-2230983

ABSTRACT

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.


Subject(s)
COVID-19 , Chitosan , Nanoparticles , Humans , Azithromycin , Powders , Administration, Inhalation , COVID-19 Drug Treatment , Respiratory Aerosols and Droplets , Particle Size
19.
Int J Environ Res Public Health ; 20(4)2023 Feb 08.
Article in English | MEDLINE | ID: covidwho-2230757

ABSTRACT

The health risk of schoolchildren who were exposed to airborne fine and ultrafine particles (PM0.1) during the COVID-19 pandemic in the Jambi City (a medium-sized city in Sumatra Island), Indonesia was examined. A questionnaire survey was used to collect information on schoolchildren from selected schools and involved information on personal profiles; living conditions; daily activities and health status. Size-segregated ambient particulate matter (PM) in school environments was collected over a period of 24 h on weekdays and the weekend. The personal exposure of PM of eight selected schoolchildren from five schools was evaluated for a 12-h period during the daytime using a personal air sampler for PM0.1 particles. The schoolchildren spent their time mostly indoors (~88%), while the remaining ~12% was spent in traveling and outdoor activities. The average exposure level was 1.5~7.6 times higher than the outdoor level and it was particularly high for the PM0.1 fraction (4.8~7.6 times). Cooking was shown to be a key parameter that explains such a large increase in the exposure level. The PM0.1 had the largest total respiratory deposition doses (RDDs), particularly during light exercise. The high level of PM0.1 exposure by indoor sources potentially associated with health risks was shown to be important.


Subject(s)
Air Pollutants , Air Pollution, Indoor , COVID-19 , Humans , Child , Particulate Matter/analysis , Air Pollutants/analysis , Indonesia , Particle Size , Air Pollution, Indoor/analysis , Pandemics , Environmental Monitoring
20.
J Radiat Res ; 64(2): 420-427, 2023 Mar 23.
Article in English | MEDLINE | ID: covidwho-2222670

ABSTRACT

Health care institutions provide prevention strategies for coronavirus disease 2019 and non-infectious disease care. We investigated the characteristics of patient contamination in a radiotherapy room by examining the trajectory and number of airborne particles in the air when talking and coughing occurred and clarified the actual state of contamination in this closed space. Aerosols were visualized and evaluated in the vertical height and head-to-tail width directions when the participant was lying on the radiotherapy tabletop. Aerosol reach was significantly greater for loud voice and coughing both at vertical height and the head-to-tail width direction. The size and number of particles around the radiotherapy tabletop were also visualized and evaluated in the radiotherapy room. The radiotherapy staff who were in the presence of the participant sometimes had many particles adhering to their facial area; particle adhesion to the staff was dominated by small size particles. Particle adherence to the irradiation device surface near the ceiling had particles larger than 1 mm. Tabletop particles tended to have a wider size range, including bigger sizes and a larger count compared to the surrounding floor. The 0.7-m radius distance from the participant's mouth tended to be highly contaminated, and the smaller the particle size, the farther it reached. The capacity to estimate areas prone to contamination can be used to predict infection of other patients and medical staff in a radiotherapy room.


Subject(s)
COVID-19 , Humans , Pilot Projects , Respiratory Aerosols and Droplets , Particle Size
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