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1.
Encyclopedia ; 1(3):773, 2021.
Article in English | ProQuest Central | ID: covidwho-1834750

ABSTRACT

DefinitionCOVID-19 mRNA vaccines contain synthetic mRNA sequences encoded for the Spike proteins expressed on the surface of SARS-CoV-2, and utilize the host cells to produce specific antigens that stimulate both humoral and cellular immunities. Lipid nanoparticles are essential to facilitate the intracellular delivery of the mRNA to its action site, the ribosome, to fully exert its effect.

2.
Powder Diffraction ; 37(1):43-46, 2022.
Article in English | ProQuest Central | ID: covidwho-1829891
3.
Environmental and Health Management of Novel Coronavirus Disease (COVID-19) ; : 325-344, 2021.
Article in English | Scopus | ID: covidwho-1827721

ABSTRACT

Avian influenzas, Ebola, Nipah, Middle East respiratory syndrome coronavirus (MERS-CoV), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is an RNA virus covered by a lipid bilayer, are directly affecting people worldwide. On the other hand, in addition to the main spread source (human contact) of SARS-CoV-2, consumers have started to think about whether foods are dangerous in terms of SARS-CoV-2 spread. The consumption of wild animals as well as the possible contamination of SARS-CoV-2 in fresh and frozen foods have caused concern and increased awareness among consumers. A heating process >70°C is being suggested to eliminate viral contamination risk. Cutting tools, slicing machines, and food-contact surfaces including stainless steel, aluminum, or glass must be regularly sanitized. The sous vide cooking method, which is based on cooking under vacuum and with pH treatments in the range of 3 and 10, could be advised in this risky period for decreasing contamination risk in food. Also, recent studies have shown that nanotechnology applications such as nanoparticles could be used to combat the SARS-CoV-2 spread, which is 50-200nm in size. Another suggested technique is cold plasma technology that could damage the protein structure of the virus. Besides these techniques, it is important to boost the immune system. In this regard, recent researches have revealed the importance of honey consumption (1g/kg per person/day), intake of vitamins, minerals like selenium, and ω-3 fatty acids. © 2021 Elsevier Inc. All rights reserved.

4.
AAPS Journal ; 24(3), 2022.
Article in English | EMBASE | ID: covidwho-1822235
5.
Journal of Experimental Nanoscience ; 17(1):297-314, 2022.
Article in English | EMBASE | ID: covidwho-1821664

ABSTRACT

A simple low-cost one-pot photodeposition synthesis with no hazardous reactants or products is used to make silver nanoparticles-activated carbon composite (SNPs@AC). The SNPs are homogenously and photodeposited and absorbed into the activated carbon matrix. Both SNPs and SNPs@AC composite have particle sizes around 10 nm and 100 nm, respectively. The SNPs@AC composite showed good antiviral activity to VERO (ATCC ccl-81) cells. Zeta potential of SNPs@AC composite is −25 mV, showing that this colloidal system is electrically stable and resistant to coagulation. For many Gram-positive and Gram-negative bacteria, the SNPs@AC composite demonstrated strong antibacterial efficacy. The SNPs@AC composite has 75.72 percent anti-inflammatory effect at concentration 500 µg/mL. This composite has a maximum non-toxic concentration (MNTC) of 78.125 g/mL, which corresponds to antiviral activity of up to 96.7 percent against hepatitis A. virus (HAV). It is suggested as a candidate for pharmaceutical formulations, such as integration into the manufacture of N95 masks for COVID-19 infection protection. Concentration 160 μg/mL SNPs@AC composite has antioxidant activity 42.74% percent. The SNPs@AC composite exhibited selective catalytic activity for the organosynthesis hydrazination reaction of 4-chloro-3, 5-di-nitro-benzo-triflouride, giving 1-hydroxy-4-nitro-6-trifluoro-methyl benzotriazole, a common antiviral drug for severe acute respiratory syndrome (SARS). SNPs@composite's well-defined pores provide suitable active sites for binding reactants: 4-Cl-3, 5-di-NO2-benzotriflouride, and hydrazine, which react to create 1-hydroxy-4-nitro-6-trifluoromethyl benzotriazole, which diffuses into solution away from the catalyst surface, leaving the catalyst surface unaffected.

6.
Journal of Immunology ; 208(6):1396-1405, 2022.
Article in English | CAB Abstracts | ID: covidwho-1818327

ABSTRACT

To develop a safe and effective nanoparticle (NP) multiepitope DNA vaccine for controlling infectious bronchitis virus (IBV) infection, we inserted the multiepitope gene expression box SBNT into a eukaryotic expression vector pcDNA3.1(+) to construct a recombinant plasmid pcDNA/SBNT. The NP multiepitope DNA vaccine pcDNA/SBNT-NPs were prepared using chitosan to encapsulate the recombinant plasmid pcDNA/SBNT, with a high encapsulation efficiency of 94.90 .. 1.35%. These spherical pcDNA/SBNT-NPs were 140.9 .. 73.2 nm in diameter, with a mean Y potential of +16.8 .. 4.3 mV. Our results showed that the chitosan NPs not only protected the plasmid DNA from DNase degradation but also mediated gene transfection in a slow-release manner. Immunization with pcDNA/SBNT-NPs induced a significant IBV-specific immune response and partially protected chickens against homologous IBV challenge. Therefore, the chitosan NPs could be a useful gene delivery system, and NP multiepitope DNA vaccines may be a potential alternative for use in the development of a novel, safe, and effective IBV vaccine.

7.
Clinical Cancer Research ; 27(6 SUPPL 1), 2021.
Article in English | EMBASE | ID: covidwho-1816923

ABSTRACT

Plant virus nanoparticles are recognized as a platform technology for potential applications in nanomedicine. While non-infectious toward mammals, many plant virus nanoparticles are recognized by the immune system and act as potent adjuvants, both in the classical setting of vaccination and cancer immunotherapy. In the context of cancer immunotherapy, we have demonstrated potent efficacy of plant virus, particularly cowpea mosaic virus (CPMV) when applied intratumorally;CPMV signals through and activates multiple toll-like receptors, which primes a potent innate immune activation leading to reprogramming of the tumor microenvironment from an immunosuppressed to immune-activated state. Data in mouse models of melanoma, colon cancer, ovarian cancer, glioma, and breast cancer demonstrate potent efficacy through priming of the innate immune system leading to adaptive and systemic anti-tumor immunity and most importantly immune memory. Efficacy was also replicated in canine patients with melanoma. Given the promise of the plant virus nanotechnology as an adjuvant for cancer immunotherapy, we also have begun to utilize the technology as a vaccination platform for the generation of COVID-19 vaccine candidates. We formulated multivalent COVID-19 vaccine candidates using plant virus nanoparticles displaying SARS-CoV-2 S protein peptide B cell epitopes. The plant virus nanoparticle confers efficient lymphatic trafficking and targeting of antigen-presenting cells;the adjuvant properties of the nanotechnology lead to robust antibody levels against the target, S protein. While other vaccine candidates have advanced through clinical testing, our approach has unique advantages: The high thermal and pH stability of the plant virus nanotechnology alleviates cold chain requirements;further, the stability of the platform technology enables its integration into vaccine delivery devices such as microneedle patches that can be shipped globally and be self-administered. In this presentation, we will discuss our data on the cancer immunotherapy and highlight the potential to pivot the technology for infectious disease vaccines with unique attributes.

8.
Chemosensors ; 10(4):136, 2022.
Article in English | ProQuest Central | ID: covidwho-1809733

ABSTRACT

In the last few decades, plasmonic colorimetric biosensors raised increasing interest in bioanalytics thanks to their cost-effectiveness, responsiveness, and simplicity as compared to conventional laboratory techniques. Potential high-throughput screening and easy-to-use assay procedures make them also suitable for realizing point of care devices. Nevertheless, several challenges such as fabrication complexity, laborious biofunctionalization, and poor sensitivity compromise their technological transfer from research laboratories to industry and, hence, still hamper their adoption on large-scale. However, newly-developing plasmonic colorimetric biosensors boast impressive sensing performance in terms of sensitivity, dynamic range, limit of detection, reliability, and specificity thereby continuously encouraging further researches. In this review, recently reported plasmonic colorimetric biosensors are discussed with a focus on the following categories: (i) on-platform-based (localized surface plasmon resonance, coupled plasmon resonance and surface lattice resonance);(ii) colloid aggregation-based (label-based and label free);(iii) colloid non-aggregation-based (nanozyme, etching-based and growth-based).

9.
Biosensors ; 12(4):253, 2022.
Article in English | ProQuest Central | ID: covidwho-1809706

ABSTRACT

Thrombin plays a central role in hemostasis and its imbalances in coagulation can lead to various pathologies. It is of clinical significance to develop a fast and accurate method for the quantitative detection of thrombin. Electrochemical aptasensors have the capability of combining the specific selectivity from aptamers with the extraordinary sensitivity from electrochemical techniques and thus have attracted considerable attention for the trace-level detection of thrombin. Nanomaterials and nanostructures can further enhance the performance of thrombin aptasensors to achieve high sensitivity, selectivity, and antifouling functions. In highlighting these material merits and their impacts on sensor performance, this paper reviews the most recent advances in label-free electrochemical aptasensors for thrombin detection, with an emphasis on nanomaterials and nanostructures utilized in sensor design and fabrication. The performance, advantages, and limitations of those aptasensors are summarized and compared according to their material structures and compositions.

10.
ACS Appl Mater Interfaces ; 2022.
Article in English | PubMed | ID: covidwho-1805548

ABSTRACT

Efficient and timely testing has taken center stage in the management, control, and monitoring of the current COVID-19 pandemic. Simple, rapid, cost-effective diagnostics are needed that can complement current polymerase chain reaction-based methods and lateral flow immunoassays. Here, we report the development of an electrochemical sensing platform based on single-walled carbon nanotube screen-printed electrodes (SWCNT-SPEs) functionalized with a redox-tagged DNA aptamer that specifically binds to the receptor binding domain of the SARS-CoV-2 spike protein S1 subunit. Single-step, reagentless detection of the S1 protein is achieved through a binding-induced, concentration-dependent folding of the DNA aptamer that reduces the efficiency of the electron transfer process between the redox tag and the electrode surface and causes a suppression of the resulting amperometric signal. This aptasensor is specific for the target S1 protein with a dissociation constant (K(D)) value of 43 ± 4 nM and a limit of detection of 7 nM. We demonstrate that the target S1 protein can be detected both in a buffer solution and in an artificial viral transport medium widely used for the collection of nasopharyngeal swabs, and that no cross-reactivity is observed in the presence of different, non-target viral proteins. We expect that this SWCNT-SPE-based format of electrochemical aptasensor will prove useful for the detection of other protein targets for which nucleic acid aptamer ligands are made available.

11.
Pandemic Outbreaks in the 21st Century: Epidemiology, Pathogenesis, Prevention, and Treatment ; : 225-233, 2021.
Article in English | Scopus | ID: covidwho-1803303

ABSTRACT

The SARS-CoV-2 (new severe acute respiratory syndrome coronavirus 2) pandemic virus has been creating devastating situations across the world and serious outbreaks have been encountering day by day since December 2019. Later, the second phase has been spread to all aged people with its moderate variants. Right from the beginning, many research groups and laboratories are desperately working for the proper solutions to eradicate the SARS-CoV-2 virus. In the year 2020 the vaccine was also developed for the COVID-19 virus from Bharat Biotech. According to the medical reports, the developed vaccine was working properly. Although in spite of having the proper results, again COVID-19 victims have been encountering every day in an uncontrolled manner. However, it has been quite interesting that currently many methodologies are available for the initial stage detection of the COVID-19 virus with accurate results. Among them, real-time polymerase chain reaction technique is gaining much attention in the research laboratories for the detection of this virus. Due to having a sophisticated procedure, a protocol for the sample preparation, and expensive instrumentation, this approach is still not available to everyone. On the other hand, nanotechnology-mediated methodologies are also providing excellent results compared to the conventional approach. Hence, in this chapter we have discussed and summarized nanotechnology-mediated recent developments, procedures, and protocols with possible working mechanisms. We believe that the provided information would be useful for the preparation of new ideas and insights to develop many innovations for the treatment and control of the SARS-CoV-2 virus. © 2021 Elsevier Inc. All rights reserved.

12.
Methods in Microbiology ; 2022.
Article in English | ScienceDirect | ID: covidwho-1797347

ABSTRACT

The outbreak of the COVID-19 pandemic in 2019 has been one of the greatest challenges modern medicine and science has ever faced. It has affected millions of people around the world and altered human life and activities as we once knew. The high prevalence as well as an extended period of incubations which usually does not present with symptoms have played a formidable role in the transmission and infection of millions. A lot of research has been carried out on developing suitable treatment and effective preventive measures for the control of the pandemic. Preventive strategies which include social distancing, use of masks, washing of hands, and contact tracing have been effective in slowing the spread of the virus;however, the infectious nature of the SARS-COV-2 has made these strategies unable to eradicate its spread. In addition, the continuous increase in the number of cases and death, as well as the appearance of several variants of the virus, has necessitated the development of effective and safe vaccines in a bid to ensure that human activities can return to normalcy. Nanotechnology has been of great benefit in the design of vaccines as nano-sized materials have been known to aid the safe and effective delivery of antigens as well as serve as suitable adjuvants to potentiate responses to vaccines. There are only four vaccine candidates currently approved for use in humans while many other candidates are at various levels of development. This review seeks to provide updated information on the current nano-technological strategies employed in the development of COVID-19 vaccines.

13.
Journal of Nanomaterials ; 2022, 2022.
Article in English | ProQuest Central | ID: covidwho-1794361

ABSTRACT

Historically, silver has been recognized as a powerful antibacterial agent with a broad spectrum of functions, and it has been employed safely in healthcare for several years. It seems that the incorporation of silver into embedded medical devices may be advantageous when particular genetic features, including such antibacterial behavior, are needed for the device to function. According to current and prior bacterial studies, it appears that the toxicity against bacteria was significantly more significant than the toxicity against human cells. Silver nanoparticles are nanoparticles with sizes ranging between one and one hundred nanometers (nm) in size. When it comes to molecular diagnostics, therapies, and equipment that are employed in a wide range of medical procedures, silver nanoparticles have a number of unique qualities that make them very useful. The physical and chemical approaches are the two majority ways for the creation of silver nanoparticles. The challenge with chemical and physical approaches is that the synthesis is complicated and can result in harmful compounds being absorbed onto the surfaces of the materials. In order to address this, the biological technique offers a viable alternative solution. Bacteria, fungus, and plant extracts are the three principal biological systems concerned in this process. A complete overview of the mechanism of action, manufacture, and uses in the medical area, as well as the healthcare and ecological concerns that are believed to be produced by these nanoparticles, is provided in this paper. The emphasis is on the proper and effective synthesis of silver nanoparticles even while exploring their numerous promising utility and attempting to assess the current status in the debates over the toxicity concerns that these nanoparticles pose, as well as attempting to reflect the needs in the debates over the toxicity concerns that these nanoparticles pose.

14.
Journal of Anatolian Environmental and Animal Sciences ; 6(4):578-584, 2021.
Article in Turkish | CAB Abstracts | ID: covidwho-1780455

ABSTRACT

Nanotechnology is the applied science of making and manipulating matter on a small scale in the range of 1-100 nm. The application of nanotechnology, particularly in vaccine science, has developed rapidly in recent years, leading to the birth of "nanovasinology". Nanotechnology is playing an increasingly important role in vaccine development, thanks to nanocarrier-based delivery systems that offer the possibility of enhancing cellular and humoral immune responses. Nanoparticle-based vaccine applications can protect vaccines from premature spoilage, increase stability, and have good adjuvant properties. NPs, with their biodegradable, minimally toxic properties, provide effective and alternative platforms to traditional vaccine methods that can be used to deliver various antigens to specific tissues and organs. Virus-like particles, liposomes, ISCOMs, polymeric inorganic nanoparticles, and emulsions;out-of-scale materials are attracting attention as potential delivery vehicles that can both stabilize vaccine antigens and act as adjuvants. The composition of the nanoparticle material plays an important role in the transport and pharmacokinetic properties of the nanoparticles, the rate of release and cellular uptake, biodegradability and biocompatibility. It is thought that nanoparticular vaccines may guide the development of vaccines for many diseases in the future, including rapidly emerging pandemics such as COVID -19 and cancers that cannot be controlled by vaccination. This review;It provides information on the physical properties of nanoparticles and nanoparticle vaccine types and reviews studies using nanoparticle-based vaccine technologies.

15.
3rd International Conference on Advances in Computing, Communication Control and Networking, ICAC3N 2021 ; : 38-42, 2021.
Article in English | Scopus | ID: covidwho-1774598

ABSTRACT

The tremendous advancements in nanotechnology have given life to the technology called Lab-on-Chip (LoC). The Nanoscale impression on semiconductors and the metals are achieved by the Lithography processes. Many of the experiments and analysis which are to be done in the laboratory have been done on this miniaturized module. The LoC technology helps to perform many laboratory functions on a single few centimeters chip size. This helps achieve high-throughput screening and automation. LoC technology requires a very less sample in drops for the analysis of the sample provided and also helps in cost effectiveness and speed response. It has great control over the concentration of samples as well as interactions to reduce the huge chemical waste. LoC through mass production aids to the development of highly compact design of systems. This paper overviews the development in the field of LoC. © 2021 IEEE.

16.
Archives of Clinical Infectious Diseases ; 16(2), 2021.
Article in English | CAB Abstracts | ID: covidwho-1771665

ABSTRACT

In the pandemic era of coronavirus disease 2019 (COVID-19), vaccines have been developed and approved to control the pandemic that might reduce the COVID-19 mortality. Transplant recipients are among the high-risk groups and are more susceptible to COVID-19 infection. According to the available data about COVID-19 vaccines, some platform technologies include vector-based, inactivated, protein subunit, virus-like particles, mRNA, and DNA vaccines (1). There are several guidelines about vaccination in immunocompromised individuals for both non-live- and live vaccines. However, there are still limited evidence-based data about COVID-19 vaccines in the hematopoietic stem cell transplantation (HSCT), and establishing a proper recommendation for vaccination in these patients would be challenging (2, 3). Transplant recipients may have shown lesser responses to the vaccines compared with the general population, and it is unknown to what extent the vaccine is effective in this group of patients. Also, in many countries, the vaccination schedule is not adjustable by the patients or physicians, and selecting a particular time window for the best efficacy of immunization is impossible. In this regard, the main concern in the patients treated with immunosuppressive drugs is not worsening symptoms and disease following vaccination. The most critical issue is determining the best time for vaccination to increase its efficacy. Here are some considerations about vector-based, inactivated, and mRNA- nanoparticle vaccines, but most evidence is not based on the results of cohort or clinical trial studies. Before HSCT, patients could receive the COVID-19 vaccine if they are not already immunosuppressed. According to evidence about other inactivated vaccines, such as the influenza vaccine, the interval to start the conditioning regimen could be considered 2 - 4 weeks following the vaccination (4). In autologous HSCT patients, COVID-19 vaccination can be considered 1 - 3 months after transplantation if there has been a community outbreak. If acquiring or transmitting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was well controlled, vaccination could be withheld after six months of transplantation. In the current pandemic, COVID-19 vaccination in allogeneic HSCT patients could be considered at least three months after transplantation. If transmission of SARS-CoV-2 was controlled, vaccination could be withheld after six months of transplantation (4-6). Vaccination of patients with chronic graft versus host disease (cGVHD) receiving less than 20 mg/day prednisolone (or equivalent) for less than 2 weeks, can be considered similar to the HSCT recipients with no GVHD (5). Vaccines in HSCT recipients with active SARS-CoV-2 infection are not effective thus, receiving the vaccine is not recommended. If an HSCT recipient has received the COVID-19 vaccine before HSCT, re-vaccination after transplantation is suggested (6). The administration of the vaccine is considered when the immune system acquired functional competence. Transplant donation should not be delayed due to the vaccination of the donor to protect the patients in case the transplant is urgent (6). It was reported that recipients who have received anti-B cell antibodies might get the vaccine at 3 - 6 months after the administration and four weeks before the next course of B cell-depleting therapy. If this time window was not possible, vaccination can be regarded under B-cell depleting therapy, considering a suboptimal response to the vaccine (7). It should be noted that the effects of rituximab may last for six months or even a year. Also, the decision to order vaccines following the use of rituximab should be based on the level of immunoglobulins and CD19. There is no strong evidence for the short duration of vaccination following the use of rituximab (such as 3 to 6 months). However, despite the low efficacy of the vaccine in such conditions, it is recommended to get the vaccine whenever available. It is reasonable that recipients who have received therapy with antithy

17.
Non-conventional in English | NTIS, Grey literature | ID: grc-753745

ABSTRACT

The overall objective of this research proposal is to conduct the initial development of a rapid circulating tumor cell-based blood test that can identify men with micrometastatic disease in order to facilitate patient selection for salvage radiotherapy. Aim 1 of this study was do perform a technical validation study and Aim 2 to embark upon testing of banked clinical specimens then to test the new assay in the setting of the NRG-GU-006 clinical trial (salvage radiotherapy /- apalutamide). In the first year of work we have begun a series of key technical validation studies while completing the sample collection from the now fully accrued NRG-GU-006 trial. Due to COVID-19 there were delays in progress but due to rapid clinical accrual and regearing of our studies, this effort is still on time.

18.
Process Biochemistry ; 2022.
Article in English | ScienceDirect | ID: covidwho-1763937

ABSTRACT

Nano Sensors are sensing devices with a dimension of less than or equal to 100nm. They are incredibly tiny devices that transform physical, chemical, or biological substances into detectable signals. Because of this device's capacity to detect physical and chemical changes, nanotechnology has emerged as a technology of choice in a variety of industries. The device provides efficient and cost-effective methods for detecting and measuring chemical and physical characteristics. This overview discusses the status of Nano Sensors, as well as their accomplishments and potential applications toward downstream targets in medical, security, agriculture as well in Covid-19 detection. The paper provides a summary and critical analysis of various architectures (structures) employed in the development and use of Nano Sensors. Surface engineering is used to generate diverse chemistries for both general and specialised purposes. We derived fresh findings from available data on the mechanism, prospective development of various structures, approaches, and applications, and highlighted the contrasts and similarities in their characteristics and working processes. The review further summarized ability and future expected of this sensor in dealing with the various challenges where different nano sensors, types, fabrication techniques and applications with highlighted novelties of these techniques and applications are presented.

19.
Economic and Social Development: Book of Proceedings ; 0:658-667, 2020.
Article in English | ProQuest Central | ID: covidwho-1762657

ABSTRACT

Working environments are continually changing as a result of the introduction of new technologies, changes in the way work is organized and shifts in economic, social and demographic conditions. We can see rapidly advancing technologies, digitalization, robotics, and the use of nanotechnology, among others, have revolutionized the workplace and have an important influence on the safety at work. The occupational and operational risks arising from driver-vehicle interaction in the field of road transport are considered to be one of the most important health and safety challenges not only for workers but also for their surroundings. Current problems of traffic and carriers, lack and aging of drivers create the need to use new technologies. Countless goods are shipped around the world every day, hundreds of goods trucks continue to flow daily between countries but the biggest contributor to this is the industry, which has been suffering from a shortage of labour for many years. Alternative vehicles with new operating parameters are coming to the market, which respond to congestion, environmental demand andfacilitate driver work. Technological developments over the last 20 years have set new standards in the area of driver-vehicle interaction. This development, socioeconomic on the one hand, technological on the other, makes automotive ergonomics: Drivervehicle interaction an important topic to explore in this area. Also coronavirus crisis is changing the world, is affecting freight - transportation business and is bringing new risks at work;some truck drivers are putting in overtime without enough protection. The article is focused on the analysis of psycho-social risks and safety problems in the work of truck drivers and modern trends of solutions, actual problems of labour market in this area such as luck of drivers and their aging.

20.
J Control Release ; 2022 Mar 28.
Article in English | MEDLINE | ID: covidwho-1763813

ABSTRACT

Acute Respiratory Distress Syndrome (ARDS), associated with Covid-19 infections, is characterized by diffuse lung damage, inflammation and alveolar collapse that impairs gas exchange, leading to hypoxemia and patient' mortality rates above 40%. Here, we describe the development and assessment of 100-nm liposomes that are tailored for pulmonary delivery for treating ARDS, as a model for lung diseases. The liposomal lipid composition (primarily DPPC) was optimized to mimic the lung surfactant composition, and the drug loading process of both methylprednisolone (MPS), a steroid, and N-acetyl cysteine (NAC), a mucolytic agent, reached an encapsulation efficiency of 98% and 92%, respectively. In vitro, treating lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages with the liposomes decreased TNFα and nitric oxide (NO) secretion, while NAC increased the penetration of nanoparticles through the mucus. In vivo, we used LPS-induced lung inflammation model to assess the accumulation and therapeutic efficacy of the liposomes in C57BL/6 mice, either by intravenous (IV), endotracheal (ET) or IV plus ET nanoparticles administrations. Using both administration methods, liposomes exhibited an increased accumulation profile in the inflamed lungs over 48 h. Interestingly, while IV-administrated liposomes distributed widely throughout the lung, ET liposomes were present in lungs parenchyma but were not detected at some distal regions of the lungs, possibly due to imperfect airflow regimes. Twenty hours after the different treatments, lungs were assessed for markers of inflammation. We found that the nanoparticle treatment had a superior therapeutic effect compared to free drugs in treating ARDS, reducing inflammation and TNFα, IL-6 and IL-1ß cytokine secretion in bronchoalveolar lavage (BAL), and that the combined treatment, delivering nanoparticles IV and ET simultaneously, had the best outcome of all treatments. Interestingly, also the DPPC lipid component alone played a therapeutic role in reducing inflammatory markers in the lungs. Collectively, we show that therapeutic nanoparticles accumulate in inflamed lungs holding potential for treating lung disorders. SIGNIFICANCE: In this study we compare intravenous versus intratracheal delivery of nanoparticles for treating lung disorders, specifically, acute respiratory distress syndrome (ARDS). By co-loading two medications into lipid nanoparticles, we were able to reduce both inflammation and mucus secretion in the inflamed lungs. Both modes of delivery resulted in high nanoparticle accumulation in the lungs, intravenously administered nanoparticles reached lung endothelial while endotracheal delivery reached lung epithelial. Combining both delivery approaches simultaneously provided the best ARDS treatment outcome.

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