THE POSSIBILITY OF USING PERFLUOROCARBON COMPOUNDS FOR VIRUS-ASSOCIATED PNEUMONIA TREATMENT

The issues of practicality in using perfluorocarbon gas transport emulsions (or pure perfluorocarbons) in severe virus-associated pneumonia treatment were considered, including those caused by coronavirus infection. Perfluorocarbons are fully fluorinated carbon compounds, on the basis of which artificial blood substitutes have been developed — gas transport perfluorocarbon emulsions for medical purposes. Perfluorocarbon emulsions were widely used in the treatment of patients in critical conditions of various genesis at the end of the last–the beginning of this century, accompanied by hypoxia, disorders of rheological properties and microcirculation of blood, perfusion of organs and tissues, intoxication, and inflammation. Large-scale clinical trials have shown a domestic plasma substitute advantage based on perfluorocarbons (perfluoroan) over foreign analogues. It is quite obvious that the inclusion of perfluorocarbon emulsions in the treatment regimens of severe virus-associated pneumonia can significantly improve this category's treatment results after analyzing the accumulated experience. A potentially useful area of therapy for acute respiratory distress syndrome is partial fluid ventilation with the use of perfluorocarbons as respiratory fluids as shown in the result of many studies on animal models and existing clinical experience. There is no gas-liquid boundary in the alveoli, as a result of which, there is an improvement in gas exchange in the lungs and a decrease in pressure in the respiratory tract when using this technique, due to the unique physicochemical properties of liquid perfluorocarbons. A promising strategy for improving liquid ventilation effectiveness using perfluorocarbon compounds is a combination with other therapeutic methods, particularly with moderate hypothermia. Antibiotics, anesthetics, vasoactive substances, or exogenous surfactant can be delivered to the lungs during liquid ventilation with perfluorocarbons, including to the affected areas, which will enhance the drugs accumulation in the lung tissues and minimize their systemic effects. However, the indications and the optimal technique for conducting liquid ventilation of the lungs in patients with acute respiratory distress syndrome have not been determined currently. Further research is needed to clarify the indications, select devices, and determine the optimal dosage regimens for perfluorocarbons, as well as search for new technical solutions for this technique The article can be used under the CC BY-NC-ND 4.0 license © Authors, 2022.

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

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

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

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

A smarter, tactical approach for combating Covid-19

As human beings, we communicate with each other just like other creatures. In the same way we need to communicate, COV-ID-19 has to communicate with other viruses. Following the latest Pandemic, combating COVID-19 has become a major need today. Several theories are being formulated and tested for the efficient prevention and treatment of the virus. Vaccination is the ultimate solution but access to the vaccine and getting vaccinated is limited. The purpose of this review paper is to present a new approach. This approach is based on the Quorum sensing of viruses like bacteria. Bacteria use this for communication and it has recently been proven for viruses too. It can be used as a new way or strategy to stop viral communication, therefore restricting the viral spread will possibly help people around the world or reduce the disease's side effects. This new tactic in-volves the use of functionalized Quantum dots nanoparticles, and when they are coupled with carbon atoms and put to use in different delivery forms, these will be useful for maximum efficacy. The use of carbon quantum dots can be useful to minimize certain possible toxic effects. This may be greatly enhanced by doping boron atoms to the structure to trigger their synergistic effects. We suggest here that the inhaler form of this proposed drug delivery system should simultaneously provide a fairly high efficiency and a less toxic solution.

Liposomal drug delivery to the lungs: a post covid-19 scenario.

High local delivery of anti-infectives to the lungs is required for activity against infections of the lungs. The present pandemic has highlighted the potential of pulmonary delivery of anti-infective agents as a viable option for infections like Covid-19, which specifically causes lung infections and mortality. To prevent infections of such type and scale in the future, target-specific delivery of drugs to the pulmonary region is a high-priority area in the field of drug delivery. The suboptimal effect of oral delivery of anti-infective drugs to the lungs due to the poor biopharmaceutical property of the drugs makes this delivery route very promising for respiratory infections. Liposomes have been used as an effective delivery system for drugs due to their biocompatible and biodegradable nature, which can be used effectively for target-specific drug delivery to the lungs. In the present review, we focus on the use of liposomal drug delivery of anti-infectives for the acute management of respiratory infections in the wake of Covid-19 infection.

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

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

Dry powder formulation of azithromycin for COVID-19 therapeutics.

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

A Monoclonal Human Alveolar Epithelial Cell Line ("Arlo") with Pronounced Barrier Function for Studying Drug Permeability and Viral Infections.

In the development of orally inhaled drug products preclinical animal models regularly fail to predict pharmacological as well as toxicological responses in humans. Models based on human cells and tissues are potential alternatives to animal experimentation allowing for the isolation of essential processes of human biology and making them accessible in vitro. Here, the generation of a novel monoclonal cell line "Arlo," derived from the polyclonal human alveolar epithelium lentivirus immortalized cell line hAELVi via single-cell printing, and its characterization as a model for the human alveolar epithelium as well as a building block for future complex in vitro models is described. "Arlo" is systematically compared in vitro to primary human alveolar epithelial cells (hAEpCs) as well as to the polyclonal hAELVi cell line. "Arlo" cells show enhanced barrier properties with high transepithelial electrical resistance (TEER) of ≈3000 Ω cm2 and a potential difference (PD) of ≈30 mV under air-liquid interface (ALI) conditions, that can be modulated. The cells grow in a polarized monolayer and express genes relevant to barrier integrity as well as homeostasis as is observed in hAEpCs. Successful productive infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a proof-of-principle study offers an additional, attractive application of "Arlo" beyond biopharmaceutical experimentation.

Pulmonary drug delivery: an effective and convenient delivery route to combat COVID-19.

The recent outbreak of coronavirus disease 2019 (COVID-19) in Wuhan, China has spread rapidly around the world, leading to a widespread and urgent effort to develop and use comprehensive approaches in the treatment of COVID-19. While oral therapy is accepted as an effective and simple method, since the primary site of infection and disease progression of COVID-19 is mainly through the lungs, inhaled drug delivery directly to the lungs may be the most appropriate route of administration. To prevent or treat primary SARS-CoV-2 infections, it is essential to target the virus port of entry in the respiratory tract and airway epithelium, which requires rapid and high-intensity inhibition or control of viral entry or replication. To achieve success in this field, inhalation therapy is the most attractive treatment approach due to efficacy/safety profiles. In this review article, pulmonary drug delivery as a unique treatment option in lung diseases will be briefly reviewed. Then, possible inhalation therapies for the treatment of symptoms of COVID-19 will be discussed and the results of clinical trials will be presented. By pulmonary delivery of the currently approved drugs for COVID-19, efficacy of the treatment would be improved along with reducing systemic side effects.

Mechanistic Modelling of Targeted Pulmonary Delivery of Dactinomycin Iron Oxide Loaded Nanoparticles for Lung Cancer Therapy.

With the increase in respiratory conditions including lung cancer post covid-19 pandemic, drug-loaded nanoparticulate dry powder inhalers (DPIs) can facilitate targeted lung delivery as a patient-friendly, non-invasive method. The aim of this work was to synthesise and optimise iron oxide nanoparticles (IONPs) containing dactinomycin as a model drug, using Quality by Design (QbD) principles. Chitosan and sodium alginate were investigated as polymeric coatings. The mass median aerodynamic diameter (MMAD), fine particle fraction (FPF), burst-effect (BE), entrapment-efficiency (EE) and the emitted-dose (ED) were investigated in initial screening studies and outcomes used to set up a Design of Experiments (DoE). Results revealed that chitosan IONPs were superior to that of sodium alginate in delivering DPI with optimal properties [ED (89.9%), FPF (59.7%), MMAD (1.59 µm) and BE (12.7%)]. Design space for targeted IONPs included formulations containing 2.1-2.5% dactinomycin and 0.5-0.9% chitosan. Differential scanning calorimetry and X-ray diffraction and SEM-EDS analysis revealed effective formation of IONPs, and TEM images revealed the production of spherical IONPs with particle size of 4.4 ± 0.77 nm. This work overcame the light sensitivity of dactinomycin to potentially target the high molecular weight drugs to the lungs, with controlled delivery based on a reduced burst effect.

Mechanisms and challenges of nanocarriers as non-viral vectors of therapeutic genes for enhanced pulmonary delivery.

With the rapid development of biopharmaceuticals and the outbreak of COVID-19, the world has ushered in a frenzy to develop gene therapy. Therefore, therapeutic genes have received enormous attention. However, due to the extreme instability and low intracellular gene expression of naked genes, specific vectors are required. Viral vectors are widely used attributed to their high transfection efficiency. However, due to the safety concerns of viral vectors, nanotechnology-based non-viral vectors have attracted extensive investigation. Still, issues of low transfection efficiency and poor tissue targeting of non-viral vectors need to be addressed. Especially, pulmonary gene delivery has obvious advantages for the treatment of inherited lung diseases, lung cancer, and viral pneumonia, which can not only enhance lung targeting and but also reduce enzymatic degradation. For systemic diseases therapy, pulmonary gene delivery can enhance vaccine efficacy via inducing not only cellular, humoral immunity but also mucosal immunity. This review provides a comprehensive overview of nanocarriers as non-viral vectors of therapeutic genes for enhanced pulmonary delivery. First of all, the characteristics and therapeutic mechanism of DNA, mRNA, and siRNA are provided. Thereafter, the advantages and challenges of pulmonary gene delivery in exerting local and systemic effects are discussed. Then, the inhalation dosage forms for nanoparticle-based drug delivery systems are introduced. Moreover, a series of materials used as nanocarriers for pulmonary gene delivery are presented, and the endosomal escape mechanisms of nanocarriers based on different materials are explored. The application of various non-viral vectors for pulmonary gene delivery are summarized in detail, with the perspectives of nano-vectors for pulmonary gene delivery.

A Review of Non-Invasive Drug Delivery through Respiratory Routes.

With rapid and non-invasive characteristics, the respiratory route of administration has drawn significant attention compared with the limitations of conventional routes. Respiratory delivery can bypass the physiological barrier to achieve local and systemic disease treatment. A scientometric analysis and review were used to analyze how respiratory delivery can contribute to local and systemic therapy. The literature data obtained from the Web of Science Core Collection database showed an increasing worldwide tendency toward respiratory delivery from 1998 to 2020. Keywords analysis suggested that nasal and pulmonary drug delivery are the leading research topics in respiratory delivery. Based on the results of scientometric analysis, the research hotspots mainly included therapy for central nervous systems (CNS) disorders (Parkinson's disease, Alzheimer's disease, depression, glioblastoma, and epilepsy), tracheal and bronchial or lung diseases (chronic obstructive pulmonary disease, asthma, acute lung injury or respiratory distress syndrome, lung cancer, and idiopathic pulmonary fibrosis), and systemic diseases (diabetes and COVID-19). The study of advanced preparations contained nano drug delivery systems of the respiratory route, drug delivery barriers investigation (blood-brain barrier, BBB), and chitosan-based biomaterials for respiratory delivery. These results provided researchers with future research directions related to respiratory delivery.

Development of Inhalable ATRA-Loaded PLGA Nanoparticles as Host-Directed Immunotherapy against Tuberculosis.

Developing new effective treatment strategies to overcome the rise in multi-drug resistant tuberculosis cases (MDR-TB) represents a global challenge. A host-directed therapy (HDT), acting on the host immune response rather than Mtb directly, could address these resistance issues. We developed an HDT for targeted TB treatment, using All Trans Retinoic Acid (ATRA)-loaded nanoparticles (NPs) that are suitable for nebulization. Efficacy studies conducted on THP-1 differentiated cells infected with the H37Ra avirulent Mycobacterium tuberculosis (Mtb) strain, have shown a dose-dependent reduction in H37Ra growth as determined by the BACT/ALERT® system. Confocal microscopy images showed efficient and extensive cellular delivery of ATRA-PLGA NPs into THP-1-derived macrophages. A commercially available vibrating mesh nebulizer was used to generate nanoparticle-loaded droplets with a mass median aerodynamic diameter of 2.13 µm as measured by cascade impaction, and a volumetric median diameter of 4.09 µm as measured by laser diffraction. In an adult breathing simulation experiment, 65.1% of the ATRA PLGA-NP dose was inhaled. This targeted inhaled HDT could offer a new adjunctive TB treatment option that could enhance current dosage regimens leading to better patient prognosis and a decreasing incidence of MDR-TB.

CFD simulation of porous microsphere particles in the airways of pulmonary fibrosis.

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.

Antivirals and the Potential Benefits of Orally Inhaled Drug Administration in COVID-19 Treatment.

Coronavirus Disease 2019 (COVID-19) pandemic has been on the agenda of humanity for more than 2 years. In the meantime, the pandemic has caused economic shutdowns, halt of daily lives and global mobility, overcrowding of the healthcare systems, panic, and worse, more than 6 million deaths. Today, there is still no specific therapy for COVID-19. Research focuses on repurposing of antiviral drugs that are licensed or currently in the research phase, with a known systemic safety profile. However, local safety profile should also be evaluated depending on the new indication, administration route and dosage form. Additionally, various vaccines have been developed. But the causative virus, Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has undergone multiple variations, too. The premise that vaccines may suffice to eradicate new and all variants is unreliable, as they are based on earlier versions of the virus. Therefore, a specific medication therapy for COVID-19 is crucial and needed in order to prevent severe complications of the disease. Even though there is no specific drug that inhibits the replication of the disease-causing virus, among the current treatment options, systemic antivirals are the most medically appropriate. As SARS-CoV-2 directly targets the lungs and initiates lung damage, treating COVID-19 with inhalants can offer many advantages over the enteral/parenteral administration. Inhaled drug delivery provides higher drug concentration, specifically in the pulmonary system. This enables the reduction of systemic side effects and produces a rapid clinical response. In this article, the most frequently (systemically) used antiviral compounds are reviewed including Remdesivir, Favipiravir, Molnupiravir, Lopinavir-Ritonavir, Umifenovir, Chloroquine, Hydroxychloroquine and Heparin. A comprehensive literature search was conducted to provide insight into the potential inhaled use of these antiviral drugs and the current studies on inhalation therapy for COVID-19 was presented. A brief evaluation was also made on the use of inhaler devices in the treatment of COVID-19. Inhaled antivirals paired with suitable inhaler devices should be considered for COVID-19 treatment options.

Pulmonary vaccine delivery: An emerging strategy for vaccination and immunotherapy

Vaccination has been known as the most successful health strategy for the prevention of infectious diseases, and their subsequent disability conditions. Conventional vaccination is based on parenteral administration and therefore requires needles, cold-chain storage and distribution. To meet these drawbacks, new strategies such as pulmonary vaccination have brought new insights into immunotherapy and vaccination. Among novel strategies, nanoparticulate vaccine delivery systems play an undeniable role in targeting and depositing of antigenic (nano-)microparticles in particular regions of the respiratory tract, engineering the inhalable powders, altering the release profile and pharmacokinetic features of vaccines. This study aims to review pulmonary immune system, pulmonary vaccine delivery, micro and nanocarriers for pulmonary vaccine delivery, and nanotechnology-based pulmonary vaccines.

Taking leads out of nature, can nano deliver us from COVID-like pandemics?

The COVID-19 crisis has alerted the research community to re-purpose scientific tools that can effectively manage emergency pandemic situations. Researchers were never so desperate to discover a 'magic bullet' that has significant clinical benefits with minimal or no side effects. At the beginning of the pandemic, due to restricted access to traditional laboratory techniques, many research groups delved into computational screening of thousands of lead molecules that could inhibit SARS-CoV-2 at one or more stages of its infectious cycle. Severalin silicostudies on natural derivatives point out their potency against SARS-CoV-2 proteins. However, theoretical predictions and existing knowledge on related molecules reflect their poor oral bioavailability due to biotransformation in the gut and liver. Nanotechnology has evolved into a key field for precise and controlled delivery of various drugs that lack aqueous solubility, have low oral bioavailability and possess pronounced toxicity in their native form. In this review, we discuss various nanoformulations of natural products with favorable ADME properties, and also briefly explore nano-drug delivery to lungs, the primary site of SARS-CoV-2 infection. Natural products are also envisioned to augment nanotechnology-based (1) personnel protective equipment forex vivoviral inactivation and (2) wearable sensors that perform rapid and non-invasive analysis of volatile organic compounds in exhaled breath of the infected person after therapeutic food consumption.

The future of dry powder inhaled therapy: Promising or discouraging for systemic disorders?

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

Lung Delivery Systems to Optimize Pharmacotherapy of COVID-19: A Concise Review

Background: COVID-19 is an ongoing viral pandemic caused by the SARS-COV-2 virus. Several drugs were repurposed for its management;however, most of these drugs were not ideal treatments by traditional methods of administration, whether given by injection or orally. This is due to many reasons including pharmacokinetic limitations or drug-induced adverse effects. There is an urgent need to develop these drugs to target the virus in the lung tissue through inhalation. Objective: To address the gap in knowledge regarding efficacy and safety of pulmonary drug delivery of repurposed antiviral against COVID-19. Findings: Ongoing trials for inhalable formulations of several drugs such as Niclosamide;Remdesivir, Hydroxychloroquine, and Azithromycin among others showed promising results. Conclusion: The development of pharmaceutical forms for inhaled administration of antiviral and anti-inflammatory drugs is an important direction that needs more attention to achieve the optimal management of respiratory infectious diseases.

Nebulizer systems: a new frontier for therapeutics and targeted delivery.

Drug delivery via the pulmonary route is a cornerstone in the pharmaceutical sector as an alternative to oral and parenteral administration. Nebulizer inhalation treatment offers multiple drug administration, easily employed with tidal breathing, suitable for children and elderly, can be adapted for severe patients and visible spray ensures patient satisfaction. This review discusses the operational and mechanical characteristics of nebulizer delivery devices in terms of aerosol production processes, their usage, benefits and drawbacks that are currently shaping the contemporary landscape of inhaled drug delivery. With the advent of particle engineering, novel inhaled nanosystems can be successfully developed to increase lung deposition and decrease pulmonary clearance. The above-mentioned advances might pave the path for treating a life-threatening disorder like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which is also discussed in the current state of the art.