Displaying publications 1 - 20 of 24 in total

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  1. Inhaled nano-based therapeutics for inflammatory lung diseases: Recent advances and future prospects
    Gulati N, Chellappan DK, MacLoughlin R, Dua K, Dureja H
    Life Sci, 2021 Nov 15;285:119969.
    PMID: 34547339 DOI: 10.1016/j.lfs.2021.119969
    Inflammatory lung diseases related morbidity and mortality impose a significant financial burden. Inflammation is a hallmark of many diseases of the respiratory system which is directly or indirectly linked to adverse health conditions, air pollution, rapid lifestyle changes, and regular outbreaks of microbial infections. The unique anatomical and physiological features of the lungs make them an ideal target organ in the treatment of inflammatory respiratory disease and with the help of inhaled therapy lungs can be targeted directly. The principal objective of this review is to present the comprehensive role of inhaled nano-based therapeutics such as liposomes, niosomes, nanoparticles, nanoemulsion, nanosuspension, and exosomes in the treatment and management of inflammatory respiratory diseases. Inhaled nanomedicines provide targeted diagnosis and treatment, improved drug solubility and distribution, prevent first-pass hepatic metabolism, improved patient compliance, and reduced drug side effects. They overcome several biological barriers in the human body and provide immediate, and quick-onset of action. Future research should be focused on improving the therapeutic efficiency of inhaled nanocarriers and to carry out in-depth mechanistic studies to translate current scientific knowledge for the efficient management of inflammatory lung diseases with minimal or no toxicity.
  2. Fulltext COVID-19 in underlying COPD Patients
    Sunkara K, Allam VR, Shukla SD, Chellappan DK, Gupta G, MacLoughlin R, et al.
    EXCLI J, 2021;20:248-251.
    PMID: 33628161 DOI: 10.17179/excli2021-3322
  3. Advances in nano-based drug delivery systems for the management of cytokine influx-mediated inflammation in lung diseases
    Gulati N, Chellappan DK, MacLoughlin R, Gupta G, Singh SK, Oliver BG, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2023 Dec 11.
    PMID: 38078921 DOI: 10.1007/s00210-023-02882-y
    Asthma, lung cancer, cystic fibrosis, tuberculosis, acute respiratory distress syndrome, chronic obstructive pulmonary disease, and COVID-19 are few examples of inflammatory lung conditions that cause cytokine release syndrome. It can initiate a widespread inflammatory response and may activate several inflammatory pathways that cause multiple organ failures leading to increased number of deaths and increased prevalence rates around the world. Nanotechnology-based therapeutic modalities such as nanoparticles, liposomes, nanosuspension, monoclonal antibodies, and vaccines can be used in the effective treatment of inflammatory lung diseases at both cellular and molecular levels. This would also help significantly in the reduction of patient mortality. Therefore, nanotechnology could be a potent platform for repurposing current medications in the treatment of inflammatory lung diseases. The aim and approach of this article are to highlight the clinical manifestations of cytokine storm in inflammatory lung diseases along with the advances and potential applications of nanotechnology-based therapeutics in the management of cytokine storm. Further in-depth studies are required to understand the molecular pathophysiology, and how nanotechnology-based therapeutics can help to effectively combat this problem.
  4. Drug delivery advances in mitigating inflammation via matrix metalloproteinases in respiratory diseases
    Mehta M, Paudel KR, Panth N, Xenaki D, Macloughlin R, Oliver BG, et al.
    Nanomedicine (Lond), 2021 03;16(6):437-439.
    PMID: 33599533 DOI: 10.2217/nnm-2021-0016
  5. Advanced drug delivery systems targeting NF-κB in respiratory diseases
    Prasher P, Sharma M, Chellappan DK, Gupta G, Jha NK, Singh SK, et al.
    Future Med Chem, 2021 07;13(13):1087-1090.
    PMID: 33947226 DOI: 10.4155/fmc-2021-0013
  6. Mitochondrial dysfunctions associated with chronic respiratory diseases and their targeted therapies: an update
    Chellappan DK, Dharwal V, Paudel KR, Jha NK, MacLoughlin R, Oliver BG, et al.
    Future Med Chem, 2021 08;13(15):1249-1251.
    PMID: 34184585 DOI: 10.4155/fmc-2021-0097
  7. Recent Trends and Applications of Nanostructure-based Drug Delivery in Alleviating Chronic Obstructive Pulmonary Disease (COPD)
    Nagar L, Gulati N, Saini A, Singh S, Gupta G, MacLoughlin R, et al.
    Curr Drug Deliv, 2024 Mar 05.
    PMID: 38445696 DOI: 10.2174/0115672018289883240226113353
    Chronic Obstructive Pulmonary Disease (COPD), a chronic lung disease that causes breathing difficulties and obstructs airflow from the lungs, has a significant global health burden and affects millions of people worldwide. The use of pharmaceuticals in COPD treatment is aimed to alleviate symptoms, improve lung function, prevent exacerbations, and enhance the overall quality of life for patients. Nanotechnology holds great promise to alleviate the burden of COPD. The main goal of this review is to present the full spectrum of therapeutics based on nanostructures for the treatment and management of COPD, including nanoparticles, polymeric nanoparticles, polymeric micelles, solid-lipid nanoparticles, liposomes, exosomes, nanoemulsions, nanosuspensions, and niosomes. Nanotechnology is just one of the many areas of research that may contribute to the development of more effective and personalized treatment modalities for COPD patients in the future. Future studies may be focused on enhancing the therapeutic effectiveness of nanocarriers by conducting extensive mechanistic investigations to translate current scientific knowledge for the effective management of COPD with little or no adverse effects.
  8. Versatility of liquid crystalline nanoparticles in inflammatory lung diseases
    Chan Y, Mehta M, Paudel KR, Madheswaran T, Panneerselvam J, Gupta G, et al.
    Nanomedicine (Lond), 2021 08;16(18):1545-1548.
    PMID: 34184917 DOI: 10.2217/nnm-2021-0114
  9. Fulltext Advances in nanotechnology-based drug delivery in targeting PI3K signaling in respiratory diseases
    Chan Y, MacLoughlin R, Zacconi FC, Tambuwala MM, Pabari RM, Singh SK, et al.
    Nanomedicine (Lond), 2021 07;16(16):1351-1355.
    PMID: 33998829 DOI: 10.2217/nnm-2021-0087
  10. Fulltext Revolutionizing polymer-based nanoparticle-linked vaccines for targeting respiratory viruses: A perspective
    Chan Y, Ng SW, Singh SK, Gulati M, Gupta G, Chaudhary SK, et al.
    Life Sci, 2021 Sep 01;280:119744.
    PMID: 34174324 DOI: 10.1016/j.lfs.2021.119744
    Viral respiratory tract infections have significantly impacted global health as well as socio-economic growth. Respiratory viruses such as the influenza virus, respiratory syncytial virus (RSV), and the recent SARS-CoV-2 infection (COVID-19) typically infect the upper respiratory tract by entry through the respiratory mucosa before reaching the lower respiratory tract, resulting in respiratory disease. Generally, vaccination is the primary method in preventing virus pathogenicity and it has been shown to remarkably reduce the burden of various infectious diseases. Nevertheless, the efficacy of conventional vaccines may be hindered by certain limitations, prompting the need to develop novel vaccine delivery vehicles to immunize against various strains of respiratory viruses and to mitigate the risk of a pandemic. In this review, we provide an insight into how polymer-based nanoparticles can be integrated with the development of vaccines to effectively enhance immune responses for combating viral respiratory tract infections.
  11. Fulltext Agarwood Oil Nanoemulsion Attenuates Cigarette Smoke-Induced Inflammation and Oxidative Stress Markers in BCi-NS1.1 Airway Epithelial Cells
    De Rubis G, Paudel KR, Manandhar B, Singh SK, Gupta G, Malik R, et al.
    Nutrients, 2023 Feb 17;15(4).
    PMID: 36839377 DOI: 10.3390/nu15041019
    Chronic obstructive pulmonary disease (COPD) is an irreversible inflammatory respiratory disease characterized by frequent exacerbations and symptoms such as cough and wheezing that lead to irreversible airway damage and hyperresponsiveness. The primary risk factor for COPD is chronic cigarette smoke exposure, which promotes oxidative stress and a general pro-inflammatory condition by stimulating pro-oxidant and pro-inflammatory pathways and, simultaneously, inactivating anti-inflammatory and antioxidant detoxification pathways. These events cause progressive damage resulting in impaired cell function and disease progression. Treatments available for COPD are generally aimed at reducing the symptoms of exacerbation. Failure to regulate oxidative stress and inflammation results in lung damage. In the quest for innovative treatment strategies, phytochemicals, and complex plant extracts such as agarwood essential oil are promising sources of molecules with antioxidant and anti-inflammatory activity. However, their clinical use is limited by issues such as low solubility and poor pharmacokinetic properties. These can be overcome by encapsulating the therapeutic molecules using advanced drug delivery systems such as polymeric nanosystems and nanoemulsions. In this study, agarwood oil nanoemulsion (agarwood-NE) was formulated and tested for its antioxidant and anti-inflammatory potential in cigarette smoke extract (CSE)-treated BCi-NS1.1 airway basal epithelial cells. The findings suggest successful counteractivity of agarwood-NE against CSE-mediated pro-inflammatory effects by reducing the expression of the pro-inflammatory cytokines IL-1α, IL-1β, IL-8, and GDF-15. In addition, agarwood-NE induced the expression of the anti-inflammatory mediators IL-10, IL-18BP, TFF3, GH, VDBP, relaxin-2, IFN-γ, and PDGF. Furthermore, agarwood-NE also induced the expression of antioxidant genes such as GCLC and GSTP1, simultaneously activating the PI3K pro-survival signalling pathway. This study provides proof of the dual anti-inflammatory and antioxidant activity of agarwood-NE, highlighting its enormous potential for COPD treatment.
  12. Role of nucleic acid-based polymeric micelles in treating lung diseases
    Kaur J, Gulati M, Corrie L, Awasthi A, Jha NK, Chellappan DK, et al.
    Nanomedicine (Lond), 2022 Oct;17(25):1951-1960.
    PMID: 36606499 DOI: 10.2217/nnm-2022-0260
    The prevalence of lung diseases is increasing year by year and existing drug therapies only provide symptomatic relief rather than targeting the actual cause. Nucleic acids can be used as an alternative therapeutic approach owing to their potential to reform a homeostatic balance by upregulating protective genes or downregulating damaging genes. However, their inherent properties, such as poor stability, ineffective cellular uptake, negative charge and so on, hinder their clinical utility. Such limitations can be overcome by exploiting the functional chemistry of polymeric micelles (PMs) for site-specific delivery, transfection efficiency and improved stability. With this objective, the present work describes the advancements made in designing nucleic acid-based PMs for treating lung diseases followed by approaches requiring consideration for clinical applications.
  13. Unwinding circular RNA's role in inflammatory pulmonary diseases
    Bhat AA, Gupta G, Goyal A, Thapa R, Almalki WH, Kazmi I, et al.
    Naunyn Schmiedebergs Arch Pharmacol, 2024 May;397(5):2567-2588.
    PMID: 37917370 DOI: 10.1007/s00210-023-02809-7
    Circular RNAs (circRNAs) have emerged as pivotal regulators of gene expression and cellular processes in various physiological and pathological conditions. In recent years, there has been a growing interest in investigating the role of circRNAs in inflammatory lung diseases, owing to their potential to modulate inflammation-associated pathways and contribute to disease pathogenesis. Inflammatory lung diseases, like asthma, chronic obstructive pulmonary disease (COPD), and COVID-19, pose significant global health challenges. The dysregulation of inflammatory responses demonstrates a pivotal function in advancing these diseases. CircRNAs have been identified as important players in regulating inflammation by functioning as miRNA sponges, engaging with RNA-binding proteins, and participating in intricate ceRNA networks. These interactions enable circRNAs to regulate the manifestation of key inflammatory genes and signaling pathways. Furthermore, emerging evidence suggests that specific circRNAs are differentially expressed in response to inflammatory stimuli and exhibit distinct patterns in various lung diseases. Their involvement in immune cell activation, cytokine production, and tissue remodeling processes underscores their possible capabilities as therapeutic targets and diagnostic biomarkers. Harnessing the knowledge of circRNA-mediated regulation in inflammatory lung diseases could lead to the development of innovative strategies for disease management and intervention. This review summarizes the current understanding of the role of circRNAs in inflammatory lung diseases, focusing on their regulatory mechanisms and functional implications.
  14. Deciphering NF-kappaB pathways in smoking-related lung carcinogenesis
    Thapa R, Moglad E, Goyal A, Bhat AA, Almalki WH, Kazmi I, et al.
    EXCLI J, 2024;23:991-1017.
    PMID: 39253534 DOI: 10.17179/excli2024-7475
    One of the main causes of death worldwide is lung cancer, which is largely caused by cigarette smoking. The crucial transcription factor NF-κB, which controls inflammatory responses and various cellular processes, is a constitutively present cytoplasmic protein strictly regulated by inhibitors like IκB proteins. Upon activation by external stimuli, it undergoes phosphorylation, translocates into the nucleus, and modulates the expression of specific genes. The incontrovertible association between pulmonary malignancy and tobacco consumption underscores and highlights a public health concern. Polycyclic aromatic hydrocarbons and nitrosamines, potent carcinogenic compounds present in the aerosol emitted from combusted tobacco, elicit profound deleterious effects upon inhalation, resulting in severe perturbation of pulmonary tissue integrity. The pathogenesis of smoking-induced lung cancer encompasses an intricate process wherein NF-κB activation plays a pivotal role, triggered by exposure to cigarette smoke through diverse signaling pathways, including those associated with oxidative stress and pro-inflammatory cytokines. Unraveling the participation of NF-κB in smoking-induced lung cancer provides pivotal insights into molecular processes, wherein intricate crosstalk between NF-κB and pathways such as MAPK and PI3K-Akt amplifies the inflammatory response, fostering an environment conducive to the formation of lung cancer. This study reviews the critical function of NF-κB in the complex molecular pathways linked to the initiation and advancement of lung carcinogenesis as well as potential treatment targets. See also the graphical abstract(Fig. 1).
  15. Rutin loaded liquid crystalline nanoparticles inhibit non-small cell lung cancer proliferation and migration in vitro
    Paudel KR, Wadhwa R, Tew XN, Lau NJX, Madheswaran T, Panneerselvam J, et al.
    Life Sci, 2021 Jul 01;276:119436.
    PMID: 33789146 DOI: 10.1016/j.lfs.2021.119436
    Non-small cell lung cancer (NSCLC) is one of the major causes of cancer-related mortality globally. Despite the availability of therapeutic options, the improvement in patient survival is yet to be achieved. Recent advances in natural product (e.g., Rutin) research, therapeutic nanotechnology and especially the combination of both could aid in achieving significant improvements in the treatment or management of NSCLC. In this study, we explore the anti-cancer activity of Rutin-loaded liquid crystalline nanoparticles (LCNs) in an in vitro model where we have employed the A549 human lung epithelial carcinoma cell line. The anti-proliferative activity was determined by MTT and Trypan blue assays, whereas, the anti-migratory activity was evaluated by the scratch wound healing assay and a modified Boyden chamber assay. We also evaluated the anti-apoptotic activity by Annexin V-FITC staining, and the colony formation activity was studied using crystal violet staining. Here, we report that Rutin-LCNs showed promising anti-proliferative and anti-migratory activities. Furthermore, Rutin-LCNs also induced apoptosis in the A549 cells and inhibited colony formation. The findings warrant further detailed and in-depth anti-cancer mechanistic studies of Rutin-LCNs with a focus towards a potential therapeutic option for NSCLC. LCNs may help to enhance the solubility of Rutin used in the treatment of lung cancer and hence enhance the anticancer effect of Rutin.
  16. Treatment of chronic airway diseases using nutraceuticals: Mechanistic insight
    Allam VSRR, Chellappan DK, Jha NK, Shastri MD, Gupta G, Shukla SD, et al.
    Crit Rev Food Sci Nutr, 2021 May 12.
    PMID: 33977840 DOI: 10.1080/10408398.2021.1915744
    Respiratory diseases, both acute and chronic, are reported to be the leading cause of morbidity and mortality, affecting millions of people globally, leading to high socio-economic burden for the society in the recent decades. Chronic inflammation and decline in lung function are the common symptoms of respiratory diseases. The current treatment strategies revolve around using appropriate anti-inflammatory agents and bronchodilators. A range of anti-inflammatory agents and bronchodilators are currently available in the market; however, the usage of such medications is limited due to the potential for various adverse effects. To cope with this issue, researchers have been exploring various novel, alternative therapeutic strategies that are safe and effective to treat respiratory diseases. Several studies have been reported on the possible links between food and food-derived products in combating various chronic inflammatory diseases. Nutraceuticals are examples of such food-derived products which are gaining much interest in terms of its usage for the well-being and better human health. As a consequence, intensive research is currently aimed at identifying novel nutraceuticals, and there is an emerging notion that nutraceuticals can have a positive impact in various respiratory diseases. In this review, we discuss the efficacy of nutraceuticals in altering the various cellular and molecular mechanisms involved in mitigating the symptoms of respiratory diseases.
  17. Fulltext Polysaccharide-Based Nanomedicines Targeting Lung Cancer
    Bhat AA, Gupta G, Alharbi KS, Afzal O, Altamimi ASA, Almalki WH, et al.
    Pharmaceutics, 2022 Dec 13;14(12).
    PMID: 36559281 DOI: 10.3390/pharmaceutics14122788
    A primary illness that accounts for a significant portion of fatalities worldwide is cancer. Among the main malignancies, lung cancer is recognised as the most chronic kind of cancer around the globe. Radiation treatment, surgery, and chemotherapy are some medical procedures used in the traditional care of lung cancer. However, these methods lack selectivity and damage nearby healthy cells. Several polysaccharide-based nanomaterials have been created to transport chemotherapeutics to reduce harmful and adverse side effects and improve response during anti-tumour reactions. To address these drawbacks, a class of naturally occurring polymers called polysaccharides have special physical, chemical, and biological characteristics. They can interact with the immune system to induce a better immunological response. Furthermore, because of the flexibility of their structures, it is possible to create multifunctional nanocomposites with excellent stability and bioavailability for the delivery of medicines to tumour tissues. This study seeks to present new views on the use of polysaccharide-based chemotherapeutics and to highlight current developments in polysaccharide-based nanomedicines for lung cancer.
  18. Agarwood oil nanoemulsion counteracts LPS-induced inflammation and oxidative stress in RAW264.7 mouse macrophages
    Malik R, Paudel KR, Manandhar B, De Rubis G, Shen J, Mujwar S, et al.
    Pathol Res Pract, 2023 Nov;251:154895.
    PMID: 37879146 DOI: 10.1016/j.prp.2023.154895
    PURPOSE: Oxidative stress and inflammation are key pathophysiological features of chronic respiratory diseases, including asthma and chronic obstructive pulmonary disease (COPD). Agarwood oil obtained from Aquilaria trees has promising antioxidant and anti-inflammatory activities. However, its clinical application is hampered by poor solubility. A viable approach to overcome this involves formulation of oily constituents into emulsions. Here, we have investigated the antioxidant and anti-inflammatory potential of an agarwood oil-based nanoemulsion (DE'RAAQSIN) against lipopolysaccharide (LPS)-induced RAW264.7 mouse macrophages in vitro.

    METHODS: The antioxidant and anti-inflammatory activity of DE'RAAQSIN was assessed by measuring the levels of ROS and nitric oxide (NO) produced, using the DCF-DA assay and the Griess reagent assay, respectively. The molecular pathways activated by DE'RAAQSIN were investigated via qPCR.

    RESULTS: LPS stimulation of RAW264.7 cells increased the production of nitric oxide (NO) and ROS and resulted in the overexpression of the inducible nitric oxide synthase (iNOS) gene. Furthermore, LPS induced the upregulation of the expression of key proinflammatory genes (IL-6, TNF-α, IL-1β, and CXCL1) and of the antioxidant gene heme oxygenase-1 (HO-1). DE'RAAQSIN demonstrated potent antioxidant and anti-inflammatory activity by significantly reducing the levels of ROS and of secreted NO, simultaneously counteracting the LPS-induced overexpression of iNOS, IL-6, TNF-α, IL-1β, and HO-1. These findings were corroborated by in silico activity prediction and physicochemical analysis of the main agarwood oil components.

    CONCLUSIONS: We propose DE'RAAQSIN as a promising alternative managing inflammatory disorders, opening the platform for further studies aimed at understanding the effectiveness of DE'RAAQSIN.

  19. Berberine-loaded engineered nanoparticles attenuate TGF-β-induced remodelling in human bronchial epithelial cells
    De Rubis G, Paudel KR, Liu G, Agarwal V, MacLoughlin R, de Jesus Andreoli Pinto T, et al.
    Toxicol In Vitro, 2023 Oct;92:105660.
    PMID: 37591407 DOI: 10.1016/j.tiv.2023.105660
    Airway remodelling occurs in chronic respiratory diseases (CRDs) such as asthma and chronic obstructive pulmonary disease (COPD). It is characterized by aberrant activation of epithelial reparation, excessive extracellular matrix (ECM) deposition, epithelial-to-mesenchymal transition (EMT), and airway obstruction. The master regulator is Transforming Growth Factor-β (TGF-β), which activates tissue repair, release of growth factors, EMT, increased cell proliferation, and reduced nitric oxide (NO) secretion. Due to its fundamental role in remodelling, TGF-β is an emerging target in the treatment of CRDs. Berberine is a benzylisoquinoline alkaloid with antioxidant, anti-inflammatory, and anti-fibrotic activities whose clinical application is hampered by poor permeability. To overcome these limitations, in this study, berberine was encapsulated in monoolein-based liquid crystalline nanoparticles (BM-LCNs). The potential of BM-LCNs in inhibiting TGF-β-induced remodelling features in human bronchial epithelial cells (BEAS-2B) was tested. BM-LCNs significantly inhibited TGF-β-induced migration, reducing the levels of proteins upregulated by TGF-β including endoglin, thrombospondin-1, basic fibroblast growth factor, vascular-endothelial growth factor, and myeloperoxidase, and increasing the levels of cystatin C, a protein whose expression was downregulated by TGF-β. Furthermore, BM-LCNs restored baseline NO levels downregulated by TGF-β. The results prove the in vitro therapeutic efficacy of BM-LCNs in counteracting TGF-β-induced remodelling features. This study supports the suitability of berberine-loaded drug delivery systems to counteract airway remodelling, with potential application as a treatment strategy against CRDs.
  20. Fulltext Berberine-loaded liquid crystalline nanoparticles inhibit non-small cell lung cancer proliferation and migration in vitro
    Paudel KR, Mehta M, Yin GHS, Yen LL, Malyla V, Patel VK, et al.
    Environ Sci Pollut Res Int, 2022 Jul;29(31):46830-46847.
    PMID: 35171422 DOI: 10.1007/s11356-022-19158-2
    Non-small cell lung cancer (NSCLC) is reported to have a high incidence rate and is one of the most prevalent types of cancer contributing towards 85% of all incidences of lung cancer. Berberine is an isoquinoline alkaloid which offers a broad range of therapeutical and pharmacological actions against cancer. However, extremely low water solubility and poor oral bioavailability have largely restricted its therapeutic applications. To overcome these limitations, we formulated berberine-loaded liquid crystalline nanoparticles (LCNs) and investigated their in vitro antiproliferative and antimigratory activity in human lung epithelial cancer cell line (A549). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), trypan blue staining, and colony forming assays were used to evaluate the anti-proliferative activity, while scratch wound healing assay and a modified Boyden chamber assay were carried out to determine the anti-migratory activity. We also investigated major proteins associated with lung cancer progression. The developed nanoparticles were found to have an average particle size of 181.3 nm with spherical shape, high entrapment efficiency (75.35%) and have shown sustained release behaviour. The most remarkable findings reported with berberine-loaded LCNs were significant suppression of proliferation, inhibition of colony formation, inhibition of invasion or migration via epithelial mesenchymal transition, and proliferation related proteins associated with cancer progression. Our findings suggest that anti-cancer compounds with the problem of poor solubility and bioavailability can be overcome by formulating them into nanotechnology-based delivery systems for better efficacy. Further in-depth investigations into anti-cancer mechanistic research will expand and strengthen the current findings of berberine-LCNs as a potential NSCLC treatment option.
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