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Biologics are a rapidly emerging class of therapeutics that have succeeded clinically and commercially due to their specificity and efficacy against various diseases including cancer, inflammatory, and autoimmune diseases. Even though most biologics are administered parenterally, nasal and pulmonary delivery would be beneficial due to numerous advantages such as being patient-friendly, noninvasive, cost-effective, and less toxic. While there are currently a few nasal and inhaled biologics on the market, for example, Suprefact®, Minirin®, Miacalcin®, most of them are designed to treat ailments related to prostate carcinoma, diabetes, osteoporosis but not for respiratory diseases. Moreover, there are some marketed nasally delivered vaccines such as Flumist® and Nasovac-S® against influenza virus, inhaled vaccines that did not make it to market. Given the rise of respiratory infections such as MERS, SARS, and SARS-CoV-2, a great deal of interest exists in developing nasal and pulmonary-delivered biologics and vaccines for respiratory diseases. The objective of this chapter is to describe the potential for pulmonary and nasal delivery of biologics. Each section delves into introducing biologics and vaccines, followed by a portrayal of recent updates on nasal and pulmonary delivery of biologics and vaccines. The most promising formulation strategies for enhancing the stability and therapeutic efficacy of biologics as a part of research and development will be discussed.

Chronic lung diseases such as asthma, chronic obstructive pulmonary disease, lung cancer, and the recently emerged COVID-19, are a huge threat to human health, and among the leading causes of global morbidity and mortality every year. Despite availability of various conventional therapeutics, many patients remain poorly controlled and have a poor quality of life. Furthermore, the treatment and diagnosis of these diseases are becoming increasingly challenging. In the recent years, the application of nanomedicine has become increasingly popular as a novel strategy for diagnosis, treatment, prevention, as well as follow-up of chronic lung diseases. This is attributed to the ability of nanoscale drug carriers to achieve targeted delivery of therapeutic moieties with specificity to diseased site within the lung, thereby enhancing therapeutic outcomes of conventional therapies whilst minimizing the risks of adverse reactions. For this instance, monoolein is a polar lipid nanomaterial best known for its versatility, thermodynamic stability, biocompatibility, and biodegradability. As such, it is commonly employed in liquid crystalline systems for various drug delivery applications. In this review, we present the applications of monoolein as a novel nanomaterial-based strategy for targeted drug delivery with the potential to revolutionize therapeutic approaches in chronic lung diseases.

Asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (CF) are major inflammatory respiratory diseases. Current mainstay therapy for asthma, and chronic obstructive pulmonary disease are corticosteroids, which have well-established side effect profiles. Phospholipids (PLs) are ubiquitous, diverse compounds with varying functions such as their structural role in the cell membrane, energy storage, and cell signaling. Recent advances in understanding PLs role as inflammatory mediators in the body as well as their widespread long-standing use as carrier molecules in drug delivery demonstrate the potential application of PLs in modulating inflammatory conditions. This review briefly explains the main mechanisms of inflammation in chronic respiratory diseases, current anti-inflammatory treatments and areas of unmet need. The structural features, roles of endogenous and exogenous phospholipids, including their use as pharmaceutical excipients, are reviewed. Current research on the immunomodulatory properties of PLs and their potential application in inflammatory diseases is the major section of this review. Considering the roles of PLs as inflammatory mediators and their safety profile established in pharmaceutical formulations, these small molecules demonstrate great potential as candidates in respiratory inflammation. Future studies need to focus on the immunomodulatory properties and the underlying mechanisms of PLs in respiratory inflammatory diseases.

There is a high incidence of upper respiratory viral infections in the human population, with infection severity being unique to each individual. Upper respiratory viruses have been associated previously with secondary bacterial infection, however, several cross-sectional studies analyzed in the literature indicate that an inverse relationship can also occur. Pathobiont abundance and/or bacterial dysbiosis can impair epithelial integrity and predispose an individual to viral infection. In this review we describe common commensal microorganisms that have the capacity to reduce the abundance of pathobionts and maintain bacterial symbiosis in the upper respiratory tract and discuss the potential and limitations of localized probiotic formulations of commensal bacteria to reduce the incidence and severity of viral infections.

This book examines numerous nanoparticle-based drug systems such as nanocrystals, dendrimers, polymeric micelles, protein-based, carbon nanotube, and liposomes that can offer advantages over traditional drug delivery systems such as ...

© Springer Nature Singapore Pte Ltd. 2020. Oxidative stress can arise from excess production of endogenous reactive oxygen species (ROS) or from exposure to exogenous ROS. In the lungs, oxidative stress causes lipid, protein and DNA oxidation, changes to histone acetylation, and inflammation. These pathways are thought to underlay the pathophysiology of respiratory diseases such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, acute respiratory distress syndrome, pneumonia, lung cancer, and obstructive sleep apnoea. This chapter discusses the risk factors for respiratory disease, the evidence for the role of oxidative stress in these diseases, and proposed antioxidant therapies for the treatment of respiratory disease.

Cell Signaling pathways form an integral part of our existence, that allows the cells to comprehend a stimulus and respond back. Such reactions, to external cues from the environment, are required and are essential to regulate the normal functioning of our body. Abnormalities in the system arise when there are errors developed in these signals, resulting in a complication or a disease. Presently, respiratory diseases contribute to being the third leading cause of morbidity worldwide. According to the current statistics, over 339 million people who are asthmatic, 65 million who are suffering from COPD, 2.3 million who are lung cancer patients and 10 million are tuberculosis patients. This toll of statistics with chronic respiratory diseases leaves a heavy burden on society and nation annual health expenditure. Hence, a better understanding of the processes governing these cellular pathways will enable us to treat and manage these deadly respiratory diseases effectively. Moreover, it is important to comprehend the synergy and interplay of the cellular signaling pathways in respiratory diseases, which will enable us to explore and develop suitable strategies for targeted drug delivery. This review, in particular, focuses on the major respiratory diseases and further provides an in-depth discussion on the various cell signaling pathways that are involved in the pathophysiology of respiratory diseases. Moreover, the review also analyses the defining concepts about advanced nano-drug delivery systems involving various nanocarriers and propose newer prospects to minimize the current challenges faced by researchers and formulation scientists.

More than half of the tailings dams worldwide contain valuable materials due to the poor performance of upstream processes. Iron ore processing plants are no exception and there has been always a transfer of iron to the tailings. This work aims to investigate the feasibility of producing a high yield product suitable for feed of the concentrate plant from the tailings dump of Zarand Steel Complex ore. For this purpose, five dumps with Fe average grade of 17-20% were studied and sampled. Six samples from each of the five dumps together with one sample from the mixture of them were taken. The representative samples were crushed by a roll crusher down to 6 mm and followed by a medium intensity magnetic separator (MIMS) and a rougher stage. The tailing of previous steps was removed and the product was concentrated by a low intensity magnetic separator (LIMS) in the cleaner stage. The product obtained was sieved by a 3 mm screen that the underflow was selected as the final product while its coarse-grained fraction was crushed by a roll crusher at the beginning of the circuit. Experimental results showed that the iron reprocessing from tailings dumps was potentially associated with an increase of 20-25% in the iron content. The mass recovery obtained from each dump sample comprised of ca. 16- 22% with the iron grade of 40-45%. The mass recovery of the mixed dumps sample was about 20% with an average grade of 40%.

Fluticasone propionate uptake in the presence of a proprietary cell-penetrating peptide (human stimulus factor, [HSF]) based on the N-terminal domain of lactoferrin was studied, alone and in combination with salmeterol, using an air interface Calu-3 epithelial model. The HSF enhanced uptake and transport of fluticasone propionate across the epithelial barrier when alone and in presence of salmeterol. This was attributed to transcellular-mediated uptake. This HSF is a promising peptide for delivery of therapeutics where enhanced epithelial penetrating is required.

Background: During implantation window, the uterine epithelium acquires a receptive phenotype and is being prepared for the initial blastocyst attachment. This unique phenomenon may stem from embryonic–maternal crosstalk utilizing an intricate language. Extracellular vesicles (EV) could be a logical mean for maternal–embryo communication. The current investigation was aimed at deciphering the main signals exchanged between the mother and the baby. Methods: The 5-ethynyl uridine (EU)-labelled trophoblast spheroids were cultivated with an endometrial cell line in a non-contact co-culturesystem.ThetrophoblastEU-labelledRNAwastrackedandcaptured in endometrial cells. The transferred labelled RNA was affinity-precipitated and purified using biotin-azide click chemistry. Total RNA-sequencing was conducted with synthesized cDNA from captured labelled and non-EU labelled RNA (background) (n=4).Differential expression analysis of RNA-seq data was performed using edgeR and limma packages to identify the transferred transcripts using differential enrichment as a proxy. The Integrative Genomics Viewer was used to validate the coverage of differentially enriched transcripts. The results were confirmed by quantitative PCR (qPCR).To establish the route of candidate RNA transfer, EVs were isolated from co-culture media using size-exclusion chromatography. Total RNA was extracted from EVs, EU-labelled RNA was affinity-precipitated and the absolute copy number of putatively transferred RNA sequences was quantified. Results: Differential enrichment analysis demonstrated that the majority of putatively transferred transcripts were non-coding RNAs derived from the mir99alet7c cluster (Chromosome 21: LINC00478). The presence of non-coding sequences from this chromosomal region in the RNA extracted from EVs was confirmed by qPCR. This suggests that these sequences are carried by throphoblast EVs. Summary/Conclusion: In this study, we showed that biorthogonal RNA labelling chemistry can be

In the past decade, an emerging process named “autophagy” has generated intense interest in many chronic lung diseases. Tissue remodeling and fibrosis is a common feature of many airway diseases, and current therapies do not prevent or reverse these structural changes. Autophagy has evolved as a conserved process for bulk degradation and recycling of cytoplasmic components to maintain basal cellular homeostasis and healthy organelle populations in the cell. Furthermore, autophagy serves as a cell survival mechanism and can also be induced by chemical and physical stress to the cell. Accumulating evidence demonstrates that autophagy plays an essential role in vital cellular processes, including tissue remodeling. This review will discuss some of the recent advancements made in understanding the role of this fundamental process in airway fibrosis with emphasis on airway remodeling, and how autophagy can be exploited as a target for airway remodeling in asthma and chronic obstructive pulmonary disease.

© 2017 Kota A et al. In the past decade, an emerging process named "autophagy" has generated intense interest in many chronic lung diseases. Tissue remodeling and fibrosis is a common feature of many airway diseases, and current therapies do not prevent or reverse these structural changes. Autophagy has evolved as a conserved process for bulk degradation and recycling of cytoplasmic components to maintain basal cellular homeostasis and healthy organelle populations in the cell. Furthermore, autophagy serves as a cell survival mechanism and can also be induced by chemical and physical stress to the cell. Accumulating evidence demonstrates that autophagy plays an essential role in vital cellular processes, including tissue remodeling. This review will discuss some of the recent advancements made in understanding the role of this fundamental process in airway fibrosis with emphasis on airway remodeling, and how autophagy can be exploited as a target for airway remodeling in asthma and chronic obstructive pulmonary disease.

© The Royal Society of Chemistry 2016. l-Leucine is used as the most common force control agent used in the inhaled dry powder formulations. In this study, the effect of l-leucine on the surface morphology, surface energy and the Young's modulus of the composite spray dried particles was studied. In addition, how l-leucine modifies the interaction of particles with a simulated pulmonary surfactant is also studied. Voriconazole (VRZ) was spray dried with different concentrations of l-leucine from hydroalcoholic solutions. Formulations were found to possess irregular morphology. Surface concentration of l-leucine was increased with increasing feed concentration and plateaued at about 20% w/w l-leucine. Atomic force microscopy (AFM) coupled with drug colloid probe enabled measurement of cohesion forces between the prepared formulations and found cohesion to be reduced significantly (p < 0.05) with the increase of l-leucine concentration. Peak Force Tapping enabled characterization of nanomechanical properties (elasticity and deformation) of formulations. Co-spray drying l-leucine with VRZ does not seem to have any influence on the Young's modulus of the formulations. Lastly, AFM revealed that the surface chemistry of the drug particle and pulmonary surfactant, as well as the contact geometry of the interacting surfaces, plays an important role in determining nature and extent of interaction between inhaled drug particles and pulmonary surfactant.