MyMedR

Targeting bacterial biofilms in pulmonary diseases in pediatric population

Dua K, Gupta G, Chellappan DK, Shukla S, Hansbro PM

Minerva Pediatr., 2018 Nov 07.

PMID: 30419743 DOI: 10.23736/S0026-4946.18.05256-8

Targeting microRNAs using nanotechnology in pulmonary diseases

Dua K, Chellappan DK, Singhvi G, de Jesus Andreoli Pinto T, Gupta G, Hansbro PM

Panminerva Med, 2018 Dec;60(4):230-231.

PMID: 30563304 DOI: 10.23736/S0031-0808.18.03459-6

Rutin loaded liquid crystalline nanoparticles inhibit lipopolysaccharide induced oxidative stress and apoptosis in bronchial epithelial cells in vitro

Paudel KR, Wadhwa R, Mehta M, Chellappan DK, Hansbro PM, Dua K

Toxicol In Vitro, 2020 Oct;68:104961.

PMID: 32771431 DOI: 10.1016/j.tiv.2020.104961

Airway inflammation and infections are the primary causes of damage in the airway epithelium, that lead to hypersecretion of mucus and airway hyper-responsiveness. The role of reactive oxygen species (ROS) and their components in the pathophysiological mechanisms of airway inflammation have been well-studied and emphasized for the past several decades. Rutin, a potent bioflavonoid, is well-known for its antioxidant, anti-inflammatory, especially in bronchial inflammation. However, poor solubility and rapid metabolism have led to its low bioavailability in biological systems, and hence limit its application. The present study aims to investigate the beneficial effects of rutin-loaded liquid crystalline nanoparticles (LCNs) against lipopolysaccharide (LPS) induced oxidative damage in human bronchial epithelial cell line (BEAS-2-B) cells in vitro. LPS was used to stimulate BEAS-2-B cells, causing the generation of nitric oxide (NO) and other reactive oxygen species (ROS) that had led to cellular apoptosis. The levels of NO and ROS were detected by, Griess reagent kit and dichlorodihydrofluorescein diacetate (DCFH-DA) respectively, whereas, cell apoptosis was studied by Annexin V-FITC and PI staining. The findings revealed that rutin-loaded LCNs significantly reduced NO, ROS levels and prevented apoptosis in BEAS-2B cells. The observations and findings provide a mechanistic understanding of the effectiveness of rutin-loaded LCNs in protecting the bronchial cells against airway inflammation, thus possessing a promising therapeutic option for the management of airway diseases.

Fulltext miRNA nanotherapeutics: potential and challenges in respiratory disorders

Mehta M, Chellappan DK, Wich PR, Hansbro NG, Hansbro PM, Dua K

Future Med Chem, 2020 06;12(11):987-990.

PMID: 32270706 DOI: 10.4155/fmc-2020-0066

Fulltext Incipient need of targeting airway remodeling using advanced drug delivery in chronic respiratory diseases

Mehta M, Satija S, Paudel KR, Liu G, Chellappan DK, Hansbro PM, et al.

Future Med Chem, 2020 05;12(10):873-875.

PMID: 32352313 DOI: 10.4155/fmc-2020-0091

Recent Advances in Oncological Submissions of Dendrimer

Soni N, Tekade M, Kesharwani P, Bhattacharya P, Maheshwari R, Dua K, et al.

Curr Pharm Des, 2017 08 30;23(21):3084-3098.

PMID: 28356042 DOI: 10.2174/1381612823666170329150201

BACKGROUND: Disseminated metastatic cancer requires insistent management owing to its reduced responsiveness for chemotherapeutic agents, toxicity to normal cells consequently lower survival rate and hampered quality of life of patients.

METHODS: Dendrimer mediated cancer therapy is advantageous over conventional chemotherapy, radiotherapy and surgical resection due to reduced systemic toxicity, and molecular level cell injury to cancerous mass, for an appreciable survival of the subject. Recently used dendrimer mediated nanotechnology for oncology aims to conquer these challenges. Dendrimers based nano-constructs are having architectures comparable to that of biological vesicles present in the human body.

RESULTS: Operating with dendrimer technology, proffers the exclusive and novel strategies with numerous applications in cancer management involving diagnostics, therapeutics, imaging, and prognostics by sub-molecular interactions. Dendrimers are designed to acquire the benefits of the malignant tumor morphology and characteristics, i.e. leaky vasculature of tumor, expression of specific cell surface antigen, and rapid proliferation.

CONCLUSION: Dendrimers mediated targeted therapy recommends innovatory function equally in diagnostics (imaging, immune-detection) as well as chemotherapy. Currently, dendrimers as nanomedicine has offered a strong assurance and advancement in drastically varying approaches towards cancer imaging and treatment. The present review discusses different approaches for cancer diagnosis and treatment such as, targeted and control therapy, photodynamic therapy, photo-thermal therapy, gene therapy, antiangiogenics therapy, radiotherapy etc.

An Overview of Circular RNAs

Awasthi R, Singh AK, Mishra G, Maurya A, Chellappan DK, Gupta G, et al.

Adv Exp Med Biol, 2018 9 28;1087:3-14.

PMID: 30259353 DOI: 10.1007/978-981-13-1426-1_1

Circular RNAs (cirRNAs) are long, noncoding endogenous RNA molecules and covalently closed continuous loop without 5'-3' polarity and polyadenylated tail which are largely concentrated in the nucleus. CirRNA regulates gene expression by modulating microRNAs and functions as potential biomarker. CirRNAs can translate in vivo to link between their expression and disease. They are resistant to RNA exonuclease and can convert to the linear RNA by microRNA which can then act as competitor to endogenous RNA. This chapter summarizes the evolutionary conservation and expression of cirRNAs, their identification, highlighting various computational approaches on cirRNA, and translation with a focus on the breakthroughs and the challenges in this new field.

Berberine loaded liquid crystalline nanostructure inhibits cancer progression in adenocarcinomic human alveolar basal epithelial cells in vitro

Mehta M, Malyla V, Paudel KR, Chellappan DK, Hansbro PM, Oliver BG, et al.

J Food Biochem, 2021 11;45(11):e13954.

PMID: 34609010 DOI: 10.1111/jfbc.13954

Metastasis represents the leading cause of death in lung cancer patients. C-X-C Motif Chemokine Ligand 8 (CXCL-8), Chemokine (C-C motif) ligand 20 (CCL-20) and heme oxygenase -1 (HO-1) play an important role in cancer cell proliferation and migration. Berberine is an isoquinoline alkaloid isolated from several herbs in the Papaveraceae family that exhibits anti-inflammatory, anticancer and antidiabetic properties. Therefore, the aim of present study is to investigate the inhibitory potential of berberine monoolein loaded liquid crystalline nanoparticles (berberine-LCNs) against cancer progression. Berberine-LCNs were prepared by mixing berberine, monoolein and poloxamer 407 (P407) using ultrasonication method. A549 cells were treated with or without 5 µM dose of berberine LCNs for 24 hr and total cellular protein was extracted and further analyzed for the protein expression of CCl-20, CXCL-8 and HO-1 using human oncology array kit. Our results showed that berberine-LCNs significantly reduced the expression of CCl-20, CXCL-8 and HO-1 at dose of 5µM. Collectively, our findings suggest that berberine-LCNs have inhibitory effect on inflammation/oxidative stress related cytokines i.e. CCL20, CXCL-8, and HO-1 which could be a novel therapeutic target for the management of lung cancer. PRACTICAL APPLICATIONS: Berberine is an isoquinoline alkaloid extracted from various plants of Papaveraceae family. CXCL-8, CCL-20 and HO-1 play an important role in cancer progression. Our study showed that Berberine LCNs significantly downregulate the expression of CXCL-8, CCL-20 and HO-1 which suggests that Berberine loaded nanoparticles could be a promising therapeutic alternative for the management of lung cancer.

Fulltext Tumor suppressor role of miR-503

Gupta G, Chellappan DK, de Jesus Andreoli Pinto T, Hansbro PM, Bebawy M, Dua K

Panminerva Med, 2018 Mar;60(1):17-24.

PMID: 29164842 DOI: 10.23736/S0031-0808.17.03386-9

MicroRNAs (miRNAs) are non-coding RNAs of around 20-25 nucleotides in length with highly conserved characteristics. They moderate post-transcriptional silencing by precisely combining with 3' untranslated regions (UTRs) of target mRNAs at a complementary site. miR‑503, an associate of the "canonical" miRNA-16 family, is expressed in numerous types of tumors such as breast cancer, prostate cancer, lung cancer, colorectal cancer, hepatocellular carcinoma, glioblastoma and several others. There is convincing evidence to show that miR‑503 functions as a tumor suppressor gene through its effects on target genes that regulate cell proliferation, migration, and invasion in tumor cells. In this current assessment, we discuss the biology and tumor suppressor role of miR‑503 in different cancers and elaborate on its mechanism of action.

Novel drug delivery approaches in treating pulmonary fibrosis

Dua K, Awasthi R, Madan JR, Chellappan DK, Nalluri BN, Gupta G, et al.

Panminerva Med, 2018 Dec;60(4):238-240.

PMID: 29480673 DOI: 10.23736/S0031-0808.18.03428-6

Fulltext Advancements in nano drug delivery systems: a challenge for biofilms in respiratory diseases

Dua K, de Jesus Andreoli Pinto T, Chellappan DK, Gupta G, Bebawy M, Hansbro PM

Panminerva Med, 2018 03;60(1):35-36.

PMID: 29370678 DOI: 10.23736/S0031-0808.18.03402-X

Nanomedicine and medicinal plants: Emerging symbiosis in managing lung diseases and associated infections

Paudel KR, De Rubis G, Panth N, Singh SK, Chellappan DK, Hansbro PM, et al.

EXCLI J, 2022;21:1299-1303.

PMID: 36483911 DOI: 10.17179/excli2022-5376

The versatility of 18ß-glycyrrhetinic acid in attenuating pulmonary inflammatory disorders

Mohamad MSB, Reyes RJ, De Rubis G, Paudel KR, Hansbro PM, Dua K, et al.

EXCLI J, 2023;22:188-190.

PMID: 36998703 DOI: 10.17179/excli2023-5845

Fulltext Cytotoxic mechanisms of berberine-phytantriol liquid crystalline nanoparticles against non-small-cell lung cancer

Paudel KR, Manandhar B, Singh SK, Gupta G, Hansbro PM, Chellappan DK, et al.

EXCLI J, 2023;22:516-519.

PMID: 37534226 DOI: 10.17179/excli2023-6156

Fulltext Berberine nanostructures attenuate ß-catenin, a key component of epithelial mesenchymal transition in lung adenocarcinoma

Malyla V, De Rubis G, Paudel KR, Chellappan DK, Hansbro NG, Hansbro PM, et al.

Naunyn Schmiedebergs Arch Pharmacol, 2023 Dec;396(12):3595-3603.

PMID: 37266589 DOI: 10.1007/s00210-023-02553-y

Lung cancer (LC) is the leading cause of cancer-related deaths globally. It accounts for more than 1.9 million cases each year due to its complex and poorly understood molecular mechanisms that result in unregulated cell proliferation and metastasis. β-Catenin is a developmentally active protein that controls cell proliferation, metastasis, polarity and cell fate during homeostasis and aids in cancer progression via epithelial-mesenchymal transition. Therefore, inhibition of the β-catenin pathway could attenuate the progression of LC. Berberine, an isoquinoline alkaloid which is known for its anti-cancer and anti-inflammatory properties, demonstrates poor solubility and bioavailability. In our study, we have encapsulated berberine into liquid crystalline nanoparticles to improve its physiochemical functions and studied if these nanoparticles target the β-catenin pathway to inhibit the human lung adenocarcinoma cell line (A549) at both gene and protein levels. We observed for the first time that berberine liquid crystalline nanoparticles at 5 µM significantly attenuate the expression of the β-catenin gene and protein. The interaction between berberine and β-catenin was further validated by molecular simulation studies. Targeting β-catenin with berberine nanoparticles represents a promising strategy for the management of lung cancer progression.

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

Targeting Cancer using Curcumin Encapsulated Vesicular Drug Delivery Systems

Hardwick J, Taylor J, Mehta M, Satija S, Paudel KR, Hansbro PM, et al.

Curr Pharm Des, 2021;27(1):2-14.

PMID: 32723255 DOI: 10.2174/1381612826666200728151610

Curcumin is a major curcuminoid present in turmeric. The compound is attributed to various therapeutic properties, which include anti-oxidant, anti-inflammatory, anti-bacterial, anti-malarial, and neuroprotection. Due to its therapeutic potential, curcumin has been employed for centuries in treating different ailments. Curcumin has been investigated lately as a novel therapeutic agent in the treatment of cancer. However, the mechanisms by which curcumin exerts its cytotoxic effects on malignant cells are still not fully understood. One of the main limiting factors in the clinical use of curcumin is its poor bioavailability and rapid elimination. Advancements in drug delivery systems such as nanoparticle-based vesicular drug delivery platforms have improved several parameters, namely, drug bioavailability, solubility, stability, and controlled release properties. The use of curcumin-encapsulated niosomes to improve the physical and pharmacokinetic properties of curcumin is one such approach. This review provides an up-to-date summary of nanoparticle-based vesicular drug carriers and their therapeutic applications. Specifically, we focus on niosomes as novel drug delivery formulations and their potential in improving the delivery of challenging small molecules, including curcumin. Overall, the applications of such carriers will provide a new direction for novel pharmaceutical drug delivery, as well as for biotechnology, nutraceutical, and functional food industries.

Advancing of Cellular Signaling Pathways in Respiratory Diseases Using Nanocarrier Based Drug Delivery Systems

Mehta M, Dhanjal DS, Satija S, Wadhwa R, Paudel KR, Chellappan DK, et al.

Curr Pharm Des, 2020;26(42):5380-5392.

PMID: 33198611 DOI: 10.2174/1381612826999201116161143

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.

Targeting respiratory diseases using miRNA inhibitor based nanotherapeutics: Current status and future perspectives

Mehta M, Satija S, Paudel KR, Malyla V, Kannaujiya VK, Chellappan DK, et al.

Nanomedicine, 2021 01;31:102303.

PMID: 32980549 DOI: 10.1016/j.nano.2020.102303

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.

Applications of drug-delivery systems targeting inflammasomes in pulmonary diseases

Devkota HP, Paudel KR, Jha NK, Gupta PK, Singh SK, Chellappan DK, et al.

Nanomedicine (Lond), 2021 11;16(27):2407-2410.

PMID: 34670398 DOI: 10.2217/nnm-2021-0275

Displaying publications 1 - 20 of 82 in total