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With an estimated failure rate of about 90%, immunotherapies that are intended for the treatment of solid tumors have caused an anomalous rise in the mortality rate over the past decades. It is apparent that resistance towards such therapies primarily occurs due to elevated levels of HIF-1 (Hypoxia-induced factor) in tumor cells, which are caused by disrupted microcirculation and diffusion mechanisms. With the advent of nanotechnology, several innovative advances were brought to the fore; and, one such promising direction is the use of perfluorocarbon nanoparticles in the management of solid tumors. Perfluorocarbon nanoparticles enhance the response of hypoxia-based agents (HBAs) within the tumor cells and have been found to augment the entry of HBAs into the tumor micro-environment. The heightened penetration of HBAs causes chronic hypoxia, thus aiding in the process of cell quiescence. In addition, this technology has also been applied in photodynamic therapy, where oxygen self-enriched photosensitizers loaded perfluorocarbon nanoparticles are employed. The resulting processes initiate a cascade, depleting tumour oxygen and turning it into a reactive oxygen species eventually to destroy the tumour cell. This review elaborates on the multiple applications of nanotechnology based perfluorocarbon formulations that are being currently employed in the treatment of tumour hypoxia.

Tobacco smoke is not only a leading cause for chronic obstructive pulmonary disease, cardiovascular disorders, and lung and oral cancers, but also causes neurological disorders such as Alzheimer ’s disease. Tobacco smoke consists of more than 4500 toxic chemicals, which form free radicals and can cross blood-brain barrier resulting in oxidative stress, an extracellular amyloid plaque from the aggregation of amyloid β (Aβ) peptide deposition in the brain. Further, respiratory infections such as Chlamydia pneumoniae, respiratory syncytial virus have also been involved in the induction and development of the disease. The necessary information collated on this review has been gathered from various literature published from 1995 to 2019. The review article sheds light on the role of smoking and respiratory infections in causing oxidative stress and neuroinflammation, resulting in Alzheimer's disease (AD). This review will be of interest to scientists and researchers from biological and medical science disciplines, including microbiology, pharmaceutical sciences and the translational researchers, etc. The increasing understanding of the relationship between chronic lung disease and neurological disease is two-fold. First, this would help to identify the risk factors and possible therapeutic interventions to reduce the development and progression of both diseases. Second, this would help to reduce the probable risk of development of AD in the population prone to chronic lung diseases.

Many plant-based bioactive compounds have been serving as the origin of drugs since long ago and many of them have been proven to have medicinal value against various chronic diseases, including, cancer, arthritis, hepatic diseases, type-2 diabetes and cardiovascular diseases. However, their clinical applications have been limited due to their poor water solubility, stability, low bioavailability and extensive transformation due to the first-pass metabolism. The applications of nanocarriers have been proven to be able to improve the delivery of bioactive phytoconstituents, resulting in the enhancement of various pharmacokinetic properties and thereby increasing the therapeutic value of phytoconstituents. These biocompatible nanocarriers also exert low toxicity to healthy cells. This review focuses on the uses and applications of different types of nanocarriers to enhance the delivery of phytoconstituents for the treatment of various chronic diseases, along with comparisons related to bioavailability and therapeutic efficacy of nano phytoconstituents with native phytoconstituents.

© 2020 Wiley Periodicals, Inc. Neutrophils are essential effector cells of immune system for clearing the extracellular pathogens during inflammation and immune reactions. Neutrophils play a major role in chronic respiratory diseases. In respiratory diseases such as asthma, chronic obstructive pulmonary disease, cystic fibrosis, lung cancer and others, there occurs extreme infiltration and activation of neutrophils followed by a cascade of events like oxidative stress and dysregulated cellular proteins that eventually result in apoptosis and tissue damage. Dysregulation of neutrophil effector functions including delayed neutropil apoptosis, increased neutrophil extracellular traps in the pathogenesis of asthma, and chronic obstructive pulmonary disease enable neutrophils as a potential therapeutic target. Accounting to their role in pathogenesis, neutrophils present as an excellent therapeutic target for the treatment of chronic respiratory diseases. This review highlights the current status and the emerging trends in novel drug delivery systems such as nanoparticles, liposomes, microspheres, and other newer nanosystems that can target neutrophils and their molecular pathways, in the airways against infections, inflammation, and cancer. These drug delivery systems are promising in providing sustained drug delivery, reduced therapeutic dose, improved patient compliance, and reduced drug toxicity. In addition, the review also discusses emerging strategies and the future perspectives in neutrophil-based therapy.

Both communicable and non-communicable chronic respiratory conditions have accorded for suffering of millions of people of all ages and stated to be leading cause of death, morbidity, economic and social pressures, and disability-adjusted life-years (DALYs) worldwide. These illnesses impair patient's health and negatively impacts families and society, particularly in low and middle-income countries. Chronic respiratory diseases (CRDs) affect different organs of respiratory system, involving airways, parenchyma, and pulmonary vasculature. As the number of respiratory diseases are exponentially escalating but still the stakeholders are not paying attention towards its serious complications. Currently, the treatment being used primarily focusses only on alleviating symptoms of these illness rather delivering the therapeutic agent at target site for optimal care and/or prevention. Lately, extensive research is being conducted on airways and systemic inflammation, oxidative stress, airway, or parenchymal rehabilitation. From which macrophages, neutrophils, and T cells, as well as structural cells as fibroblasts, epithelial, endothelial, and smooth muscle cells have been found to be active participants that are involved in these chronic respiratory diseases. The pathogenesis of all these chronic respiratory diseases gets caused differently via mediators and proteins, including cytokines, chemokines, growth factors and oxidants. Presently, the target of prescription therapies is to reduce the inflammation of airways and relieve the airway contraction. In all studies, cytokines have been found to play an imperative role in fostering chronic airway inflammation and remodelling. Owing to the limitations of conventional treatments, the current review aims to summarize the current knowledge about the chronic respiratory disease and discuss further about the various conventional methods that can be used for treating this ailment. Additionally, it also highlights and discusses about the advanced drug delivery system that are being used for targeting the interleukins for the treatment of CRDs.

The challenges and difficulties associated with conventional drug delivery systems have led to the emergence of novel, advanced targeted drug delivery systems. Therapeutic drug delivery of proteins and peptides to the lungs is complicated owing to the large size and polar characteristics of the latter. Nevertheless, the pulmonary route has attracted great interest today among formulation scientists, as it has evolved into one of the important targeted drug delivery platforms for the delivery of peptides, and related compounds effectively to the lungs, primarily for the management and treatment of chronic lung diseases. In this review, we have discussed and summarized the current scenario and recent developments in targeted delivery of proteins and peptide-based drugs to the lungs. Moreover, we have also highlighted the advantages of pulmonary drug delivery over conventional drug delivery approaches for peptide-based drugs, in terms of efficacy, retention time and other important pharmacokinetic parameters. The review also highlights the future perspectives and the impact of targeted drug delivery on peptide-based drugs in the coming decade.

Nuclear factor κB (NFκB) is a unique protein complex that plays a major role in lung inflammation and respiratory dysfunction. The NFκB signaling pathway, therefore becomes an avenue for the development of potential pharmacological interventions, especially in situations where chronic inflammation is often constitutively active and plays a key role in the pathogenesis and progression of the disease. NFκB decoy oligodeoxynucleotides (ODNs) are double-stranded and carry NFκB binding sequences. They prevent the formation of NFκB-mediated inflammatory cytokines and thus have been employed in the treatment of a variety of chronic inflammatory diseases. However, the systemic administration of naked decoy ODNs restricts their therapeutic effectiveness because of their poor pharmacokinetic profile, instability, degradation by cellular enzymes and their low cellular uptake. Both structural modification and nanotechnology have shown promising results in enhancing the pharmacokinetic profiles of potent therapeutic substances and have also shown great potential in the treatment of respiratory diseases such as asthma, chronic obstructive pulmonary disease and cystic fibrosis. In this review, we examine the contribution of NFκB activation in respiratory diseases and recent advancements in the therapeutic use of decoy ODNs. In addition, we also highlight the limitations and challenges in use of decoy ODNs as therapeutic molecules, cellular uptake of decoy ODNs, and the current need for novel delivery systems to provide efficient delivery of decoy ODNs. Furthermore, this review provides a common platform for discussion on the existence of decoy ODNs, as well as outlining perspectives on the latest generation of delivery systems that encapsulate decoy ODNs and target NFκB in respiratory diseases.

The incidence of diabetes has increased globally in recent years and figures of diabetic patients were estimated to rise up to 642 million by 2040. The disorder is accompanied with various complications if not managed at the early stages, and interlinked high mortality rate and morbidity with time. Different classes of drugs are available for the management of type 2 diabetes but were having certain limitations of their safety. Alphaglucosidase is a family of enzyme originated from the pancreas which plays a role in the anabolism of 80-90% of carbohydrate consumed into glucose. This glucose is absorbed into the blood and results in frank postprandial hyperglycemia and worsens the conditions of diabetic patients which precipitate complications. Inhibition of these enzymes helps to prevent postprandial hyperglycemia and the formation of glycated end products. Alphaglucosidase inhibitors are reported to be more important in adequate control of type 2, but marketed drugs have various side effects, such as poor patient compliance and also expensive. This proves the needs for other class of drugs with better efficacy, safety, patient compliance and economic. In this review, we have emphasized the recent advances in the field of new alpha-glucosidase inhibitors with improved safety and pharmacological profile.

Hypoxia inducible factor (HIF)-prolyl hydroxylase (PHD) inhibitors are shown to be protective in several models of inflammatory bowel disease (IBD). However, these non-selective inhibitors are known to inhibit all the three isoforms of PHD, i.e. PHD-1, PHD-2 and PHD-3. In the present report, we investigated the associated changes in levels of PHDs during the development and recovery of chemically induced colitis in mice. The results indicated that in the experimental model of murine colitis, levels of both, PHD-1 and PHD-2 were found to be increased with the progression of the disease; however, the level of PHD-3 remained the same in group of healthy controls and mice with colitis. Thus, the findings advocated that inhibitors, which inhibited all three isoforms of PHD could not be ideal therapeutics for IBD since PHD-3 is required for normal gut function. Hence, this necessitates the development of new compounds capable of selectively inhibiting PHD-1 and PHD-2 for effective treatment of IBD.

Oligonucleotide-based therapies are advanced novel interventions used in the management of various respiratory diseases such as asthma and Chronic Obstructive Pulmonary Disease (COPD). These agents primarily act by gene silencing or RNA interference. Better methodologies and techniques are the need of the hour that can deliver these agents to tissues and cells in a target specific manner by which their maximum potential can be reached in the management of chronic inflammatory diseases. Nanoparticles play an important role in the target-specific delivery of drugs. In addition, oligonucleotides also are extensively used for gene transfer in the form of polymeric, liposomal and inorganic carrier materials. Therefore, the current review focuses on various novel dosage forms like nanoparticles, liposomes that can be used efficiently for the delivery of various oligonucleotides such as siRNA and miRNA. We also discuss the future perspectives and targets for oligonucleotides in the management of respiratory diseases., Highlights • Oligonucleotides are polynucleic acids consists of five base pairs. • They act by altering gene expression of an affected individual. • In respiratory diseases they are emerging as a newer therapy.

Lung diseases are the leading cause of mortality worldwide. The currently available therapies are not sufficient, leading to the urgent need for new therapies with sustained anti-inflammatory effects. Small/short or silencing interfering RNA (siRNA) has potential therapeutic implications through post-transcriptional downregulation of the target gene expression. siRNA is essential in gene regulation, so is more favorable over other gene therapies due to its small size, high specificity, potency, and no or low immune response. In chronic respiratory diseases, local and targeted delivery of siRNA is achieved via inhalation. The effectual delivery can be attained by the generation of aerosols via inhalers and nebulizers, which overcomes anatomical barriers, alveolar macrophage clearance and mucociliary clearance. In this review, we discuss the different siRNA nanocarrier systems for chronic respiratory diseases, for safe and effective delivery. siRNA mediated pro-inflammatory gene or miRNA targeting approach can be a useful approach in combating chronic respiratory inflammatory conditions and thus providing sustained drug delivery, reduced therapeutic dose, and improved patient compliance. This review will be of high relevance to the formulation, biological and translational scientists working in the area of respiratory diseases.

© 2019 The Author(s). Background: High rates of preterm births remain a UK public health concern. Preterm birth is a major determinant of adverse infant and longer-term outcomes, including survival, quality of life, psychosocial effects on the family and health care costs. We aim to test whether a model of care combining continuity of midwife care with rapid referral to a specialist obstetric clinic throughout pregnancy, intrapartum and the postpartum period is feasible and improves experience and outcomes for women at increased risk of preterm birth. Methods: This pilot, hybrid, type 2 randomised controlled implementation trial will recruit 350 pregnant women at increased risk of preterm birth to a midwifery continuity of care intervention or standard care. The intervention will be provided from recruitment (antenatal), labour, birth and the postnatal period, in hospital and community settings and in collaboration with specialist obstetric clinic care, when required. Standard care will be the current maternity care provision by NHS midwives and obstetricians at the study site. Participants will be followed up until 6-8 weeks postpartum. The composite primary outcome is the appropriate initiation of any specified interventions related to the prevention and/or management of preterm labour and birth. Secondary outcomes are related to: recruitment and attrition rates; implementation; acceptability to women, health care professionals and stakeholders; health in pregnancy and other complications; intrapartum outcomes; maternal and neonatal postnatal outcomes; psycho-social health; quality of care; women's experiences and health economic analysis. The trial has 80% power to detect a 15% increase in the rate of appropriate interventions (40 to 55%). The analysis will be by 'intention to treat' analysis. Discussion: Little is known about the underlying reasons why and how models of midwifery continuity of care are associated with fewer preterm births, better maternal and infant outcomes and more positive experiences; nor how these models of care can be implemented successfully in the health services. This will be the first study to provide direct evidence regarding the effectiveness, implementation and evaluation of a midwifery continuity of care model and rapid access to specialist obstetric services for women at increased risk of preterm birth. Trial registration: ISRCTN37733900. Retrospectively registered on 21 August 2017.

Oxidative stress is intensely involved in enhancing the severity of various chronic respiratory diseases (CRDs) including asthma, chronic obstructive pulmonary disease (COPD), infections and lung cancer. Even though there are various existing anti-inflammatory therapies, which are not enough to control the inflammation caused due to various contributing factors such as anti-inflammatory genes and antioxidant enzymes. This leads to an urgent need of novel drug delivery systems to combat the oxidative stress. This review gives a brief insight into the biological factors involved in causing oxidative stress, one of the emerging hallmark feature in CRDs and particularly, highlighting recent trends in various novel drug delivery carriers including microparticles, microemulsions, microspheres, nanoparticles, liposomes, dendrimers, solid lipid nanocarriers etc which can help in combating the oxidative stress in CRDs and ultimately reducing the disease burden and improving the quality of life with CRDs patients. These carriers improve the pharmacokinetics and bioavailability to the target site. However, there is an urgent need for translational studies to validate the drug delivery carriers for clinical administration in the pulmonary clinic.

Nowadays, respiratory diseases have become the major cause of health care burded and death worldwide. According to the WHO, pulmonary disease holds the third position for mortality and supplement the development of antimicrobial resistance among immune-compromised patience are increasing the complication in health. Approximately, 65 million people are suffering from chronic obstructive pulmonary disease, 334 million are suffering from asthma, 10 million are suffering from tuberculosis, and 2.3 million are suffering from lung cancer. Different conventional methods have been used to treat these diseases, but certain limitations of conventional therapy limit their efficacy and efficiency. Hence, this leads to the exploitation of new therapeutic approaches as conventional approaches are not that much effective. Among the available alternatives, the targeted nanodrug delivery system (NDDS) has gained significant attention concerning their ability, activity, and tolerability to control these pulmonary diseases. Additionally, NDDS has associated advantages like a controlled deposition, controlled release of drugs and appropriate size for systemic and local treatment. This chapter plans to highlight the efficacy and physiological aspects of the targeted drug delivery, mechanism of pulmonary drug administration. Moreover, it will also discuss the different nanocarriers for drug delivery. As a better insight into the challenges and complications associated with developing the pulmonary disease will propose new opportunities to pharmacists to minimize the medical and technical gaps.

The highly contagious coronavirus, which had already affected more than 2 million people in 210 countries, triggered a colossal economic crisis consequently resulting from measures adopted by various goverments to limit transmission. This has placed the lives of many people infected worldwide at great risk. Currently there are no established or validated treatments for COVID-19, that is approved worldwide. Nanocarriers may offer a wide range of applications that could be developed into risk-free approaches for successful therapeutic strategies that may lead to immunisation against the severe acute respiratory syndrome coronavirus 2 (SARS‑CoV‑2) which is the primary causative organism that had led to the current COVID-19 pandemic. We address existing as well as emerging therapeutic and prophylactic approaches that may enable us to effectively combat this pandemic, and also may help to identify the key areas where nano-scientists can step in.

MicroRNAs (miRNAs) play a fundamental role in the developmental and physiological processes that occur in both animals and plants. AntagomiRs are synthetic antagonists of miRNA, which prevent the target mRNA from suppression. Therapeutic approaches that modulate miRNAs have immense potential in the treatment of chronic respiratory disorders. However, the successful delivery of miRNAs/antagomiRs to the lungs remains a major challenge in clinical applications. A range of materials, namely, polymer nanoparticles, lipid nanocapsules and inorganic nanoparticles, has shown promising results for intracellular delivery of miRNA in chronic respiratory disorders. This review discusses the current understanding of miRNA biology, the biological roles of antagomiRs in chronic respiratory disease and the recent advances in the therapeutic utilization of antagomiRs as disease biomarkers. Furthermore our review provides a common platform to debate on the nature of antagomiRs and also addresses the viewpoint on the new generation of delivery systems that target antagomiRs in respiratory 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.

Pancreatic cancer is one of the fatal causes of global cancer-related deaths. Although surgery and chemotherapy are standard treatment options, post-treatment outcomes often end in a poor prognosis. In the present study, we investigated anti-pancreatic cancer and amelioration of radiation-induced oxidative damage by crocin. Crocin is a carotenoid isolated from the dietary herb saffron, a prospect for novel leads as an anti-cancer agent. Crocin significantly reduced cell viability of BXPC3 and Capan-2 by triggering caspase signaling via the downregulation of Bcl-2. It modulated the expression of cell cycle signaling proteins P53, P21, P27, CDK2, c-MYC, Cyt-c and P38. Concomitantly, crocin treatment-induced apoptosis by inducing the release of cytochrome c from mitochondria to cytosol. Microarray analysis of the expression signature of genes induced by crocin showed a substantial number of genes involved in cell signaling pathways and checkpoints (723) are significantly affected by crocin. In mice bearing pancreatic tumors, crocin significantly reduced tumor burden without a change in body weight. Additionally, it showed significant protection against radiation-induced hepatic oxidative damage, reduced the levels of hepatic toxicity and preserved liver morphology. These findings indicate that crocin has a potential role in the treatment, prevention and management of pancreatic cancer.

Cancer continues to be one of the most challenging diseases to be treated and is one of the leading causes of deaths around the globe. Cancers account for 13% of all deaths each year, with cancer-related mortality expected to rise to 13.1 million by the year 2030. Although, we now have a large library of chemotherapeutic agents, the problem of non-selectivity remains the biggest drawback, as these substances are toxic not only to cancerous cells, but also to other healthy cells in the body. The limitations with chemotherapy and radiation have led to the discovery and development of novel strategies for safe and effective treatment strategies to manage the menace of cancer. Researchers have long justified and have shed light on the emergence of nanotechnology as a potential area for cancer therapy and diagnostics, whereby, nanomaterials are used primarily as nanocarriers or as delivery agents for anticancer drugs due to their tumor targeting properties. Furthermore, nanocarriers loaded with chemotherapeutic agents also overcome biological barriers such as renal and hepatic clearances, thus improving therapeutic efficacy with lowered morbidity. Theranostics, which is the combination of rationally designed nanomaterials with cancer-targeting moieties, along with protective polymers and imaging agents has become one of the core keywords in cancer research. In this review, we have highlighted the potential of various nanomaterials for their application in cancer therapy and imaging, including their current state and clinical prospects. Theranostics has successfully paved a path to a new era of drug design and development, in which nanomaterials and imaging contribute to a large variety of cancer therapies and provide a promising future in the effective management of various cancers. However, in order to meet the therapeutic needs, theranostic nanomaterials must be designed in such a way, that take into account the pharmacokinetic and pharmacodynamics properties of the drug for the development of effective carcinogenic therapy.

Introduction: Pulmonary route is one of the preferred routes for the administration of therapeutically active agents for systemic as well as localized delivery. Chronic obstructive pulmonary disease (COPD), bronchial asthma, pneumonia, pulmonary hypertension, bronchiolitis, lung cancer, and tuberculosis are the major chronic diseases associated with the pulmonary system. Knowledge about the affecting factors, namely, the etiology, pathophysiology, and the various barriers (mechanical, chemical, immunological, and behavioral) in pulmonary drug delivery is essential to develop an effective drug delivery system. Formulation strategies and mechanisms of particle deposition in the lungs also play an important role in designing a suitable delivery system.Areas covered: In the present paper, various drug delivery strategies, viz. nanoparticles, microparticles, liposomes, powders, and microemulsions have been discussed systematically, from a patent perspective.Expert opinion: Patent publications on formulation strategies have been instrumental in the evolution of new techniques and technologies for safe and effective treatment of pulmonary diseases. New delivery systems are required to be simple/reproducible/scalable/cost-effective scale for manufacturing ability and should be safe/effective/stable/controllable for meeting quality and regulatory compliance.

The apparent predicament of the representative chemotherapy for managing respiratory distress calls for an obligatory deliberation for identifying the pharmaceuticals that effectively counter the contemporary intricacies associated with target disease. Multiple, complex regulatory pathways manifest chronic pulmonary disorders, which require chemotherapeutics that produce composite inhibitory effect. The cost effective natural product based molecules hold a high fervor to meet the prospects posed by current respiratory-distress therapy by sparing the tedious drug design and development archetypes, present a robust standing for the possible replacement of the fading practice of poly-pharmacology, and ensure the subversion of a potential disease relapse. This study summarizes the experimental evidences on natural products moieties and their components that illustrates therapeutic efficacy on respiratory disorders., Highlights • Plant derived therapeutics for managing chronic respiratory disorders. • Activity of natural product based molecules on key regulatory pathways of COPD. • Preclinical evidence for the efficacy of natural product moieties. • Clinical significance of plant derived molecules in pulmonary distress.

Ethnopharmacological relevance Epilepsy is one of the most commonly occurring non-communicable neurological disorder that affects people of all age groups. Around 50 million people globally are epileptic, with 80% cases in developing countries due to lack of access to treatments determined by high cost and poor availability or it can be defined by the fraction of active epileptic patients who are not appropriately being treated. The availability of antiepileptic drugs and their adjuvant therapy in such countries is less than 50% and these are highly susceptible to drug interactions and severe adverse effects. As a result, the use of herbal medicine is increasingly becoming popular. Aim of the study To provide pharmacological information on the active constituents evaluated in the preclinical study to treat epilepsy with potential to be used as an alternative therapeutic option in future. It also provides affirmation for the development of novel antiepileptic drugs derived from medicinal plants. Materials and methods Relevant information on the antiepileptic potential of phytoconstituents in the preclinical study (in-vitro, in-vivo) is provided based on their effect on screening parameters. Besides, relevant information on pharmacology of phytoconstituents, the traditional use of their medicinal plants related to epilepsy and status of phytoconstituents in the clinical study were derived from online databases, including PubMed, Clinicaltrial. gov, The Plant List (TPL, www.theplantlist.org ), Science Direct. Articles identified using preset searching syntax and inclusion criteria are presented. Results More than 70% of the phytoconstituents reviewed in this paper justified the traditional use of their medicinal plant related to epilepsy by primarily acting on the GABAergic system. Amongst the phytoconstituents, only cannabidiol and tetrahydrocannabinol have been explored for clinical application in epilepsy. Conclusion The preclinical and clinical data of the phytoconstituents to treat epilepsy and its associated comorbidities provides evidence for the discovery and development of novel antiepileptic drugs from medicinal plants. In terms of efficacy and safety, further randomized and controlled clinical studies are required to understand the complete pharmacodynamic and pharmacokinetic picture of phytoconstituents. Also, specific botanical source evaluation is needed.

Respiratory disorders, especially non-communicable, chronic inflammatory diseases, are amongst the leading causes of mortality and morbidity worldwide. Respiratory diseases involve multiple pulmonary components, including airways and lungs that lead to their abnormal physiological functioning. Several signaling pathways have been reported to play an important role in the pathophysiology of respiratory diseases. These pathways, in addition, become the compounding factors contributing to the clinical outcomes in respiratory diseases. A range of signaling components such as Notch, Hedgehog, Wingless/Wnt, bone morphogenetic proteins, epidermal growth factor and fibroblast growth factor is primarily employed by these pathways in the eventual cascade of events. The different aberrations in such cell-signaling processes trigger the onset of respiratory diseases making the conventional therapeutic modalities ineffective. These challenges have prompted us to explore novel and effective approaches for the prevention and/or treatment of respiratory diseases. In this review, we have attempted to deliberate on the current literature describing the role of major cell signaling pathways in the pathogenesis of pulmonary diseases and discuss promising advances in the field of therapeutics that could lead to novel clinical therapies capable of preventing or reversing pulmonary vascular pathology in such patients.

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 are asthmatic, 65 million are suffering from COPD, 2.3 million 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 the nation's 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.

Regardless of advances in detection and treatment, breast cancer affects about 1.5 million women all over the world. Since the last decade, genome-wide association studies (GWAS) have been extensively conducted for breast cancer to define the role of miRNA as a tool for diagnosis, prognosis and therapeutics. MicroRNAs are small, non-coding RNAs that are associated with the regulation of key cellular processes such as cell multiplication, differentiation, and death. They cause a disturbance in the cell physiology by interfering directly with the translation and stability of a targeted gene transcript. MicroRNAs (miRNAs) constitute a large family of non-coding RNAs, which regulate target gene expression and protein levels that affect several human diseases and are suggested as the novel markers or therapeutic targets, including breast cancer. MicroRNA (miRNA) alterations are not only associated with metastasis, tumor genesis but also used as biomarkers for breast cancer diagnosis or prognosis. These are explained in detail in the following review. This review will also provide an impetus to study the role of microRNAs in breast cancer.

Cancer has been one of the leading causes of death worldwide. In 2018, 17 million new cases of cancer have been reported across the world, which resulted in 9.6 million deaths. Continued efforts have been made to achieve effective progress in treatment of the disease. Conventional cancer therapy has various drawbacks like lack of specificity, resistance toward therapy, drug-related toxicities, patient noncompliance, etc. To overcome these limitations, there is a need to shift toward advanced nanotechnology-based therapeutic agents to improve efficacy, safety, and patient compliance. Nanotechnology is interdisciplinary and involves application of materials science, medicine, biotechnology and engineering, and aiming for advancement in cancer treatment and diagnosis. In addition, nanocarriers such as quantum dots, dendrimers, liposomes, micelles, lipid nanoparticles (NPs), carbon nanotubes, gold (Au) NPs, etc. have taken treatment and diagnosis one step ahead and have proven to be beneficial in reducing side effects and drug-related toxicities. Theranostic nanocarriers are also an emerging field in cancer therapeutics, performing imaging, diagnosis, and simultaneous treatment. NPs are smart carriers designed to particularly release drug at the tumor site, resulting in increased bioavailability of the drug. This targeted delivery is achieved by exploiting the unique characteristics of tumor cells called enhanced permeability and retention (EPR) effect. Surface functionalization of nanocarriers with ligand moiety increases drug uptake inside tumor cells; this phenomenon is generally referred to as active targeting. Conjugation of ligands that are highly expressed in a particular cancer can assist to achieve cellular targeting. Among various nanocarrier systems that are designed to treat cancer, only a limited number of them have been reported to enter the clinical trials. In this chapter, we have focused in detailed recent advances in cancer therapy. We have discussed briefly regarding clinically approved products and nanoformulations undergoing clinical trials. Efforts have also been made by industry and regulatory agencies to commercialize nanomedicine from clinical stage. We have also discussed briefly regarding the important steps required to be taken by formulation scientist for development of these new generation advanced formulations.

Insulin resistance along with type 2 diabetes (T2D) is some of the complications of obesity. Insulin resistance occurs due to the increased discharge of fatty acids, lipids, and other advancing factors, by the adipose tissue, leading to a myriad of complications. Several other substances namely glycerol, enzymes, inflammatory factors, and hormones are also involved in the overall mechanism. At the point when resistance towards insulin occurs, along with abnormally functioning β-cells, the overall burden of the inability to control elevated glucose levels in the blood ensues. Anomalies in β-cell are thus more critical in the development of T2D and its related symptoms. This information is encouraging investigation of the molecular and hereditary basis of the ailment and new ways to deal with its management and avoidance.

Pulmonary inflammation has become the hallmark for various respiratory diseases like acute respiratory syndrome (ARDS), asthma, chronic obstructive respiratory disease (COPD), and lung cancer. These diseases are now becoming a major health problem and burden on the aging population. To treat these disease antiinflammatory drugs are used, which reduces the chances of pulmonary inflammation. Due to the side effects of the allopathic drug, there has been a paradigm shift toward herbal medicine as they are safe and don’t have any side effect. Now, herbal medicine has gained the same attention as the ancient time all around the world. But the delivery system employed for administrating these herbal drugs is outdated and has reduced efficiency. Moreover, advancement in nanotechnology has enhanced the delivery of the medicine and the release of the therapeutic drug at the targeted site. Hence, this multidisciplinary approach is an effective way to bridge the gap between the material and medicinal science to develop a promising therapeutic solution. The benefits of using this nanocarrier system involve easy amendment of these nanocarriers, minimized drug degradation, and delivery of more amount of drug at the targeted site. This book chapter aims to discuss plant based nanocarrier systems that are effective in treating respiratory diseases.

A large population, including people of all age groups, is suffering from chronic respiratory diseases worldwide. Asthma, chronic obstructive pulmonary disease, occupational lung diseases, cystic fibrosis, etc. are the most common of these diseases and are noncurable with conventional and currently available therapies. Nanotechnology is emerging as a great therapeutic promise in different spheres including drug delivery systems and is becoming the technology of choice nowadays. The administration of drugs via inhalation helps in avoiding the first-pass metabolism by targeted delivery to the affected site. It has been observed that there is a huge diversity in nanotechnology being used in pulmonary diseases, and thus safety assessment is a challenging as well as important task. The present review focuses on some of the major emerging nanotechnologies for chronic pulmonary diseases and includes some of the latest studies in the field of nanomedicines.

Aging is one of the principal risk factors that play an important role in several human conditions and pathogenesis, primarily neurodegenerative disorders, such as amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Alzheimer’s disease (AD). A progressive loss of neurons, reduced motor or behavioral functions, and abnormally aggregated proteins define these conditions. An unbalanced redox environment, including the generation of excessive reactive oxygen species (ROS) or system deficiency, causes oxidative stress (OS). The brain is one of the principal organs that are particularly susceptible to ROS because of its elevated oxygen demand and the presence of abundant peroxidation-sensitive lipid cells. Previous studies have reported that widespread neurodegenerative disease pathophysiology involves OS. Cellular antioxidants are known to alter such redox status, target destruction, and regulate oxidative mechanisms engaged in cell proliferation, gene expression, signal transduction, and cell death pathway. Oxidants and antioxidants are important in maintaining free balance, metabolized, environmental-related radicals and the body’s antioxidant mechanisms. In biological systems, several complex natural antioxidant mechanisms occur that work together to prevent prooxidant damage. The objective of this chapter is to demonstrate that free radicals are engaged in neurodegenerative disease pathophysiology and that antioxidants and scavenging products help in the prevention and cure of such disease conditions. This chapter also examines the role of antioxidants in neurodegenerative illnesses, in their chemoprevention and therapy.

Multiple therapeutics options are available for the management of nonsmall cell lung cancer (NSCLC) in recent years, along with a better understanding of cancer biology. These therapies can be broadly classified as chemotherapy, immunotherapy, targeted therapy, and combination therapy. Chemotherapy is the first treatment option used in the advanced stage of the disease, showing beneficial activity for patients compared with palliative care. Among chemotherapy, research has been done and going on to explore the beneficial activity of cisplatin, gemcitabine, paclitaxel, docetaxel, carboplatin, and doxorubicin. Immunotherapy is a potential therapeutic option for lung cancer patients with robust results and multiple evidence of positive response during trial and treatments. For immunotherapy, various immune checkpoint inhibitors such as nivolumab, pembrolizumab, durvalumab, atezolizumab, and avelumab targeting programmed cell death protein 1/program cell death-ligand one pathway are in a clinical trial. Due to the recognition of various oncogenic drivers, novel targeted therapies are being investigated and established. These therapies are crucial in the management of particular patients and can be given as first-line therapy too. In targeted therapy, alectinib, ceritinib, and lorlatinib target ALK gene, whereas crizotinib targets ROS1 gene, and afatinib, erlotinib, and gefitinib target EGFR gene. Likewise, multiple drugs are administered as a combination therapy such as carboplatin-paclitaxel and cisplatin-etoposide-irinotecan, and nivolumab with platinum doublet therapy is used in lung cancer for better outcomes, synergistic effects, and reduced adverse side effects. In this book chapter, we will discuss all of these four treatment options highlighting the latest research, including clinical trials, animal studies, and in vitro studies. Our information aims to alter the paradigm on the treatment of lung cancer and highlight the fact that upcoming novel treatments are promising with many benefits for patients.

© 2019 Elsevier B.V. Cancer is one of the major diseases that cause a high number of deaths globally. Of the major types of cancers, lung cancer is known to be the most chronic form of cancer in the world. The conventional management of lung cancer includes different medical interventions like chemotherapy, surgical removal, and radiation therapy. However, this type of approach lacks specificity and also harms the adjacent normal cells. Lately, nanotechnology has emerged as a promising intervention in the management and treatment of lung cancers. Nanotechnology has revolutionized the existing modalities and focuses primarily on reducing toxicity and improving the bioavailability of anticancer drugs to the target tumor cells. Nanocarrier systems are being currently used extensively to exploit and to overcome the obstructions induced by cancers in the lungs. The nano-carrier-loaded therapeutic drug delivery methods have shown promising potential in treating lung cancer as its target is to control the growth of tumor cells. In this review, various modes of nano drug delivery options like liposomes, dendrimers, quantum dots, carbon nanotubes and metallic nanoparticles have been discussed. Nano-carrier drug delivery systems emerge as a promising approach and thus is expected to provide newer and advanced avenues in cancer therapeutics.

Macrophages are considered as the most flexible cells of the hematopoietic system that are distributed in the tissues to act against pathogens and foreign particles. Macrophages are essential in maintaining homeostatic tissue processes, repair and immunity. Also, play important role in cytokine secretion and signal transduction of the infection so as to develop acquired immunity. Accounting to their involvement in pathogenesis, macrophages present a therapeutic target for the treatment of inflammatory respiratory diseases. This review focuses on novel drug delivery systems (NDDS) including nanoparticles, liposomes, dendrimers, microspheres etc that can target alveolar macrophage associated with inflammation, intracellular infection and lung cancer. The physiochemical properties and functional moieties of the NDDS attributes to enhanced macrophage targeting and uptake. The NDDS are promising for sustained drug delivery, reduced therapeutic dose, improved patient compliance and reduce drug toxicity. Further, the review also discuss about modified NDDS for specificity to the target and molecular targeting via anti-microbial peptides, kinases, NRF-2 and phosphodiesterase.

Eosinophils are bi-lobed, multi-functional innate immune cells with diverse cell surface receptors that regulate local immune and inflammatory responses. Several inflammatory and infectious diseases are triggered with their build up in the blood and tissues. The mobilization of eosinophils into the lungs is regulated by a cascade of processes guided by Th2 cytokine generating T-cells. Recruitment of eosinophils essentially leads to a characteristic immune response followed by airway hyperresponsiveness and remodeling, which are hallmarks of chronic respiratory diseases. By analysing the dynamic interactions of eosinophils with their extracellular environment, which also involve signaling molecules and tissues, various therapies have been invented and developed to target respiratory diseases. Having entered clinical testing, several eosinophil targeting therapeutic agents have shown much promise and have further bridged the gap between theory and practice. Moreover, researchers now have a clearer understanding of the roles and mechanisms of eosinophils. These factors have successfully assisted molecular biologists to block specific pathways in the growth, migration and activation of eosinophils. The primary purpose of this review is to provide an overview of the eosinophil biology with a special emphasis on potential pharmacotherapeutic targets. The review also summarizes promising eosinophil-targeting agents, along with their mechanisms and rationale for use, including those in developmental pipeline, in clinical trials, or approved for other respiratory disorders.

Chronic airway inflammatory diseases are characterized by persistent proinflammatory responses in the respiratory tract. Although, several treatment strategies are currently available, lifelong therapy is necessary for most of these diseases. In recent years, phytophenols, namely, flavonoids, derived from fruits and vegetables have been gaining tremendous interest and have been extensively studied due to their low toxicological profile. Naringenin is a bioflavonoid abundantly found in citrus fruits. This substance has shown notable therapeutic potential in various diseases due to its promising diverse biological activities. In this review, we have attempted to review the published studies from the available literature, discussing the molecular level mechanisms of naringenin in different experimental models of airway inflammatory diseases including asthma, chronic obstructive pulmonary disease (COPD), lung cancer, pulmonary fibrosis and cystic fibrosis. Current evidences have proposed that the anti-inflammatory properties of naringenin play a major role in ameliorating inflammatory disease states. In addition, naringenin also possesses several other biological properties. Despite the proposed mechanisms suggesting remarkable therapeutic benefits, the clinical use of naringenin is, however, hampered by its low solubility and bioavailability. Furthermore, this review also discusses on the studies that utilise nanocarriers as a drug delivery system to address the issue of poor solubility.

Tuberculosis (caused by Mycobacterium tuberculosis, Mtb) treatment involves multiple drug regimens for a prolonged period. However, the therapeutic benefit is often limited by poor patient compliance, subsequently leading to treatment failure and development of antibiotic resistance. Notably, oxidative stress is a crucial underlying factor that adversely influences the various treatment regimens in tuberculosis. Little information is available with advanced drug delivery systems that could be effectively utilized, in particular, for targeting the oxidative stress in tuberculosis. Thus, this presents an opportunity to review the utility of various available, controlled-release drug delivery systems (e.g., microspheres, liposomes, niosomes, solid lipid nanoparticles, dendrimers) that could be beneficial in tuberculosis treatments. This will help the biological and formulation scientists to pave a new path in formulating a treatment regimen for multi-drug resistant Mtb.

Submitral aneurysms of the left ventricle were first reported from Nigeria and other African nations [1]. Several reports from Indian centers of small numbers of cases have highlighted their presentation with left ventricular dysfunction, heart failure and mitral regurgitation with poor outcome both on medical and surgical management [2, 3, 4]. We report two cases who had presented to our centre in the last six months, highlighting the wide spectrum in the presentation and outcome in this rare disease.