Publications by authors named "Harish Dureja"

87 Publications

Inhaled nano-based therapeutics for inflammatory lung diseases: Recent advances and future prospects.

Life Sci 2021 Sep 18:119969. Epub 2021 Sep 18.

Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak 124001, India. Electronic address:

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.
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http://dx.doi.org/10.1016/j.lfs.2021.119969DOI Listing
September 2021

Advances in pulmonary drug delivery targeting microbial biofilms in respiratory diseases.

Nanomedicine (Lond) 2021 09 5;16(21):1905-1923. Epub 2021 Aug 5.

Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, NSW, 2007, Australia.

The increasing burden of respiratory diseases caused by microbial infections poses an immense threat to global health. This review focuses on the various types of biofilms that affect the respiratory system and cause pulmonary infections, specifically bacterial biofilms. The article also sheds light on the current strategies employed for the treatment of such pulmonary infection-causing biofilms. The potential of nanocarriers as an effective treatment modality for pulmonary infections is discussed, along with the challenges faced during treatment and the measures that may be implemented to overcome these. Understanding the primary approaches of treatment against biofilm infection and applications of drug-delivery systems that employ nanoparticle-based approaches in the disruption of biofilms are of utmost interest which may guide scientists to explore the vistas of biofilm research while determining suitable treatment modalities for pulmonary respiratory infections.
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http://dx.doi.org/10.2217/nnm-2021-0057DOI Listing
September 2021

Emerging cases of mucormycosis under COVID-19 pandemic in India: Misuse of antibiotics.

Drug Dev Res 2021 Jul 29. Epub 2021 Jul 29.

Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, New South Wales, Australia.

COVID-19's second wave had a significant impact on India, on May 7, 2021, the largest daily recorded case count was a little more than 4 million, and it has since fallen. Although the number of new cases reported has dropped, during the third week of May 2021, India accounted for about 45% of new cases identified globally and around 34% of deaths. As India maintains its present level of stability, a new urgent threat has emerged in the form of coronavirus-associated mucormycosis. Mucormycosis, an acute and deadly fungal infection caused by Mucorales-related fungal species, is a fungal emergency with a particularly aggressive propensity for contiguous spread, associated with a poor prognosis if not properly and immediately identified, and treated. Mucormycosis, sometimes referred to as the "black fungus," has increased more rapidly in India during the second wave of COVID-19 than during the first wave, with at least 14,872 cases as of May 28, 2021. Uncontrolled diabetic mellitus (DM) and other immunosuppressive diseases such as neutropenia and corticosteroid treatment have traditionally been identified as risk factors for mucormycosis. Therefore, the use of glucocorticoids or high doses of glucocorticoids in mild COVID-19 cases (without hypoxemia) should be avoided. In addition, drugs that target the immune pathway, such as tocilizumab, are not recommended without clear benefits.
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http://dx.doi.org/10.1002/ddr.21862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8426670PMC
July 2021

Bracing NK cell based therapy to relegate pulmonary inflammation in COVID-19.

Heliyon 2021 Jul 21;7(7):e07635. Epub 2021 Jul 21.

Department of Biotechnology, School of Engineering &Technology, Sharda University, Greater Noida, Uttar Pradesh, 201310, India.

The contagiosity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has startled mankind and has brought our lives to a standstill. The treatment focused mainly on repurposed immunomodulatory and antiviral agents along with the availability of a few vaccines for prophylaxis to vanquish COVID-19. This seemingly mandates a deeper understanding of the disease pathogenesis. This necessitates a plausible extrapolation of cell-based therapy to COVID-19 and is regarded equivalently significant. Recently, correlative pieces of clinical evidence reported a robust decline in lymphocyte count in severe COVID-19 patients that suggest dysregulated immune responses as a key element contributing to the pathophysiological alterations. The large granular lymphocytes also known as natural killer (NK) cells play a heterogeneous role in biological functioning wherein their frontline action defends the body against a wide array of infections and tumors. They prominently play a critical role in viral clearance and executing immuno-modulatory activities. Accumulated clinical evidence demonstrate a decrease in the number of NK cells in circulation with or without phenotypical exhaustion. These plausibly contribute to the progression of pulmonary inflammation in COVID-19 pneumonia and result in acute lung injury. In this review, we have outlined the present understanding of the immunological response of NK cells in COVID-19 infection. We have also discussed the possible use of these powerful biological cells as a therapeutic agent in view of preventing immunological harms of SARS-CoV-2 and the current challenges in advocating NK cell therapy for the same.
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http://dx.doi.org/10.1016/j.heliyon.2021.e07635DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8294777PMC
July 2021

Effects of curcumin-loaded poly(lactic-co-glycolic acid) nanoparticles in MDA-MB231 human breast cancer cells.

Nanomedicine (Lond) 2021 08 23;16(20):1763-1773. Epub 2021 Jul 23.

Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, NSW 2007, Australia.

This study was aimed at evaluating the anticancer potential of curcumin-loaded poly(lactic-co-glycolic acid) (PLGA) based nanoparticles (NPs) in MDA-MB231 human breast cancer cells. Curcumin-loaded PLGA NPs were developed using a modified solvent evaporation technique. Physical characterization was performed on the formulated NPs. Furthermore, experiments were conducted to study the biological activity of the curcumin-loaded NPs. Curcumin-loaded PLGA NPs demonstrated high encapsulation efficiency and sustained payload release. Moreover, the NPs exhibited a significant reduction in cell viability, cell migration and cell invasion in the MDA-MB231 cells. The study revealed that the formulated curcumin-loaded PLGA NPs possessed significant anti-metastatic properties. The findings showcased the possible potential of curcumin-loaded NPs in the management of debilitating conditions such as cancer. In addition, this study could form the basis for further research and advancements in this area.
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http://dx.doi.org/10.2217/nnm-2021-0066DOI Listing
August 2021

Sorafenib for hepatocellular carcinoma: potential molecular targets and resistance mechanisms.

J Chemother 2021 Jul 22:1-16. Epub 2021 Jul 22.

Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, India.

Hepatocellular carcinoma (HCC) is the most widespread typical therapy-resistant, unresectable type of malignant solid tumour with a high death rate constituting huge medical concern. Sorafenib is a small molecule oral multi-target kinase potent inhibitor that acts by suppressing/blocking the multiplication of the tumour cells, angiogenesis, and encouraging apoptosis of the tumour cells. Though, the precise mechanism of tumour cell death induction by sorafenib is yet under exploration. Furthermore, genetic heterogeneity plays a critical role in developing sorafenib resistance, which leads the way to identify the need for predictive biomarkers responsible for drug resistance. Therefore, it is essential to find out the fundamental resistance mechanisms to expand therapeutic plans. The authors summarize the molecular concepts of resistance, progression, potential molecular targets, HCC management therapies, and discussion on the advancements expected in the coming future, inclusive of biomarker-driven treatment strategies, which may provide the prospects to design innovative therapeutically targeted strategies for the HCC treatment and the clinical implementation of emerging targeted agents.
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http://dx.doi.org/10.1080/1120009X.2021.1955202DOI Listing
July 2021

Targeting LIN28: a new hope in prostate cancer theranostics.

Future Oncol 2021 07 15. Epub 2021 Jul 15.

School of Pharmacy & Pharmaceutical Sciences, Ulster University, Coleraine, County Londonderry, Northern Ireland BT52 1SA, UK.

The mortality and morbidity rates for prostate cancer have recently increased to alarming levels, rising higher than lung cancer. Due to a lack of drug targets and molecular probes, existing theranostic techniques are limited. Human LIN28A and its paralog LIN28B overexpression are associated with a number of tumors resulting in a remarkable increase in cancer aggression and poor prognoses. The current review aims to highlight recent work identifying the key roles of LIN28A and LIN28B in prostate cancer, and to instigate further preclinical and clinical research in this important area.
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http://dx.doi.org/10.2217/fon-2021-0247DOI Listing
July 2021

Role of chitosan based nanomedicines in the treatment of chronic respiratory diseases.

Int J Biol Macromol 2021 Aug 8;185:20-30. Epub 2021 Jun 8.

Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak 124001, India. Electronic address:

Chitosan-loaded nanomedicines provide a greater opportunity for the treatment of respiratory diseases. Natural biopolymer chitosan and its derivatives have a large number of proven pharmacological actions like antioxidant, wound healing, immuno-stimulant, hypocholesterolemic, antimicrobial, obesity treatment, anti-inflammatory, anticancer, bone tissue engineering, antifungal, regenerative medicine, anti-diabetic and mucosal adjuvant, etc. which attracted its use in the pharmaceutical industry. As compared to other polysaccharides, chitosan has excellent mucoadhesive characteristics, less viscous, easily modified into the chemical and biological molecule and gel-forming property due to which the drugs retain in the respiratory tract for a longer period of time providing enhanced therapeutic action of the drug. Chitosan-based nanomedicines would have the greatest effect when used to transport poor water soluble drugs, macromolecules like proteins, and peptides through the lungs. In this review, we highlight and discuss the role of chitosan and its nanomedicines in the treatment of chronic respiratory diseases such as pneumonia, asthma, COPD, lung cancer, tuberculosis, and COVID-19.
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http://dx.doi.org/10.1016/j.ijbiomac.2021.06.035DOI Listing
August 2021

Middle East Respiratory Syndrome (MERS) Virus-Pathophysiological Axis and the Current Treatment Strategies.

AAPS PharmSciTech 2021 Jun 8;22(5):173. Epub 2021 Jun 8.

Department of Life Sciences, International Medical University, Bukit Jalil, 57000, Kuala Lumpur, Malaysia.

Middle East respiratory syndrome (MERS) is a lethal respiratory disease with its first case reported back in 2012 (Jeddah, Saudi Arabia). It is a novel, single-stranded, positive-sense RNA beta coronavirus (MERS-CoV) that was isolated from a patient who died from a severe respiratory illness. Later, it was found that this patient was infected with MERS. MERS is endemic to countries in the Middle East regions, such as Saudi Arabia, Jordan, Qatar, Oman, Kuwait and the United Arab Emirates. It has been reported that the MERS virus originated from bats and dromedary camels, the natural hosts of MERS-CoV. The transmission of the virus to humans has been thought to be either direct or indirect. Few camel-to-human transmissions were reported earlier. However, the mode of transmission of how the virus affects humans remains unanswered. Moreover, outbreaks in either family-based or hospital-based settings were observed with high mortality rates, especially in individuals who did not receive proper management or those with underlying comorbidities, such as diabetes and renal failure. Since then, there have been numerous reports hypothesising complications in fatal cases of MERS. Over the years, various diagnostic methods, treatment strategies and preventive measures have been strategised in containing the MERS infection. Evidence from multiple sources implicated that no treatment options and vaccines have been developed in specific, for the direct management of MERS-CoV infection. Nevertheless, there are supportive measures outlined in response to symptom-related management. Health authorities should stress more on infection and prevention control measures, to ensure that MERS remains as a low-level threat to public health.
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http://dx.doi.org/10.1208/s12249-021-02062-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8186825PMC
June 2021

Harnessing amphiphilic polymeric micelles for diagnostic and therapeutic applications: Breakthroughs and bottlenecks.

J Control Release 2021 06 19;334:64-95. Epub 2021 Apr 19.

Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India; Centre of Excellence in Nanoscience & Technology, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India.

Amphiphilic block copolymers are widely utilized in the design of formulations owing to their unique physicochemical properties, flexible structures and functional chemistry. Amphiphilic polymeric micelles (APMs) formed from such copolymers have gained attention of the drug delivery scientists in past few decades for enhancing the bioavailability of lipophilic drugs, molecular targeting, sustained release, stimuli-responsive properties, enhanced therapeutic efficacy and reducing drug associated toxicity. Their properties including ease of surface modification, high surface area, small size, and enhanced permeation as well as retention (EPR) effect are mainly responsible for their utilization in the diagnosis and therapy of various diseases. However, some of the challenges associated with their use are premature drug release, low drug loading capacity, scale-up issues and their poor stability that need to be addressed for their wider clinical utility and commercialization. This review describes comprehensively their physicochemical properties, various methods of preparation, limitations followed by approaches employed for the development of optimized APMs, the impact of each preparation technique on the physicochemical properties of the resulting APMs as well as various biomedical applications of APMs. Based on the current scenario of their use in treatment and diagnosis of diseases, the directions in which future studies need to be carried out to explore their full potential are also discussed.
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http://dx.doi.org/10.1016/j.jconrel.2021.04.014DOI Listing
June 2021

Calcium sensing receptor hyperactivation through viral envelop protein E of SARS CoV2: A novel target for cardio-renal damage in COVID-19 infection.

Drug Dev Res 2021 09 9;82(6):784-788. Epub 2021 Mar 9.

School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, Jaipur, India.

Over the recent decades, a number of new pathogens have emerged within specific and diverse populations across the globe, namely, the Nipah virus, the Ebola virus, the Zika virus, and coronaviruses (CoVs) to name a few. Recently, a new form of coronavirus was identified in the city of Wuhan, China. Interestingly, the genomic architecture of the virus did not match with any of the existing genomic sequencing data of previously sequenced CoVs. This had led scientists to confirm the emergence of a new CoV strain. Originally, named as 2019-nCoV, the strain is now called as SARS-CoV-2. High serum levels of proinflammatory mediators, namely, interleukin-12 (IL-12), IL-1β, IL-6, interferon-gamma (IFNγ), chemoattractant protein-1, and IFN-inducible protein, have been repeatedly observed in subjects who were infected with this virus. In addition, the virus demonstrated strong coagulation activation properties, leading to further the understanding on the SARS-CoV2. To our understanding, these findings are unique to the published literature. Numerous studies have reported anomalies, namely, decline in the number of lymphocytes, platelets and albumins; and a rise in neutrophil count, aspartate transaminase, alanine aminotransaminase, lactate dehydrogenase, troponins, creatinine, complete bilirubin, D-dimers, and procalcitonin. Supplementation of calcium during the SARS CoV-2 associated hyperactive stage of calcium-sensing receptors (CaSR) may be harmful to the cardio-renal system. Thus, pharmacological inhibition of CaSR may prevent the increase in the levels of intracellular calcium, oxidative, inflammatory stress, and cardio-renal cellular apoptosis induced by high cytokines level in COVID-19 infection.
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http://dx.doi.org/10.1002/ddr.21810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8250664PMC
September 2021

An overview of vaccine development for COVID-19.

Ther Deliv 2021 03 24;12(3):235-244. Epub 2021 Feb 24.

School of Pharmacy & Pharmaceutical Sciences, Ulster University, Coleraine, County Londonderry, Northern Ireland, BT52 1SA, UK.

The COVID-19 pandemic continues to endanger world health and the economy. The causative SARS-CoV-2 coronavirus has a unique replication system. The end point of the COVID-19 pandemic is either herd immunity or widespread availability of an effective vaccine. Multiple candidate vaccines - peptide, virus-like particle, viral vectors (replicating and nonreplicating), nucleic acids (DNA or RNA), live attenuated virus, recombinant designed proteins and inactivated virus - are presently under various stages of expansion, and a small number of vaccine candidates have progressed into clinical phases. At the time of writing, three major pharmaceutical companies, namely Pfizer and Moderna, have their vaccines under mass production and administered to the public. This review aims to investigate the most critical vaccines developed for COVID-19 to date.
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http://dx.doi.org/10.4155/tde-2020-0129DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923686PMC
March 2021

Formulation, Characterisation and In vitro Cytotoxic Effect of Lens culinaris Medikus Seeds Extract Loaded Chitosan Microspheres.

Curr Mol Pharmacol 2021 ;14(3):448-457

Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, Haryana, India.

Objective: The aim of present study was to formulate chitosan microspheres loaded with ethanolic extract of Lens culinaris Medikus (L.culinaris) seeds (ME) and to explore its anticancer potential against lung cancer (A549) cell line.

Methods: Central composite design was applied to prepare and optimise the chitosan microspheres. The prepared microspheres were evaluated for its physicochemical characterisation, in vitro drug release and anti-cancer potential in vitro.

Results: L.culinaris loaded chitosan microspheres were prepared successfully with suitable particle size, entrapment efficiency and drug release. The developed ME were spherical shaped with the particle size of 2.08 μm. The drug entrapment efficiency and cumulative drug release was found 1.58±0.02% and 81.95±0.35%, respectively. Differential scanning calorimetry studies revealed no interaction between drugs and polymers used. The cytotoxic effect of the optimised formulation revealed a significant response as compared to the ethanolic extract of L.culinaris seeds (IC: 22.56 μg/ml vs. 63.58 μg/ml), which was comparable to that of reference drug, doxorubicin (22 μg/ml). These observations demonstrate that the optimised microspheres are effective against lung cancer (A549) cells.

Conclusion: The significant cytotoxic response of the developed microspheres may be attributed due to its low particle size, high entrapment efficiency and prolonged drug release profile.
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http://dx.doi.org/10.2174/1874467214666210210124739DOI Listing
January 2021

Rutin-loaded liquid crystalline nanoparticles attenuate oxidative stress in bronchial epithelial cells: a PCR validation.

Future Med Chem 2021 03 4;13(6):543-549. Epub 2021 Feb 4.

Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, NSW 2007, Australia.

In the present study, the inhibitory potential of rutin-loaded liquid crystalline nanoparticles (LCNs) on oxidative stress was determined in human bronchial epithelial cells (BEAS-2B) by analysing the expression levels of different antioxidant (NADPH quinine oxidoreductase-1 (); γ-glutamyl cysteine synthetase catalytic subunit ()) and pro-oxidant (NADPH oxidase ; ) genes. Our findings revealed that the rutin-loaded LCNs inhibited the genes, namely  and , which caused oxidative stress. In addition, these nanoparticles demonstrated an upregulation in the expression of the antioxidant genes  and in a dose-dependent manner. The study indicates the promising potential of rutin-loaded LCNs as an effective treatment strategy in patients with high oxidant loads in various respiratory diseases.
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http://dx.doi.org/10.4155/fmc-2020-0297DOI Listing
March 2021

Hypoxia-Inducible Factor (HIF): Fuel for Cancer Progression.

Curr Mol Pharmacol 2021 ;14(3):321-332

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara-144411, Punjab, India.

Hypoxia is an integral part of the tumor microenvironment, caused primarily due to rapidly multiplying tumor cells and a lack of proper blood supply. Among the major hypoxic pathways, HIF-1 transcription factor activation is one of the widely investigated pathways in the hypoxic tumor microenvironment (TME). HIF-1 is known to activate several adaptive reactions in response to oxygen deficiency in tumor cells. HIF-1 has two subunits, HIF-1β (constitutive) and HIF-1α (inducible). The HIF-1α expression is largely regulated via various cytokines (through PI3K-ACT-mTOR signals), which involves the cascading of several growth factors and oncogenic cascades. These events lead to the loss of cellular tumor suppressant activity through changes in the level of oxygen via oxygen-dependent and oxygen-independent pathways. The significant and crucial role of HIF in cancer progression and its underlying mechanisms have gained much attention lately among the translational researchers in the fields of cancer and biological sciences, which have enabled them to correlate these mechanisms with various other disease modalities. In the present review, we have summarized the key findings related to the role of HIF in the progression of tumors.
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http://dx.doi.org/10.2174/1874467214666210120154929DOI Listing
January 2021

Evidence of Coronavirus (CoV) Pathogenesis and Emerging Pathogen SARS-CoV-2 in the Nervous System: A Review on Neurological Impairments and Manifestations.

J Mol Neurosci 2021 Jan 19. Epub 2021 Jan 19.

Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute (HMRI), University of Newcastle, New Lambton Heights, Newcastle, NSW, 2305, Australia.

The coronavirus disease 2019 (COVID-19) pandemic is an issue of global significance that has taken the lives of many across the world. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for its pathogenesis. The pulmonary manifestations of COVID-19 have been well described in the literature. Initially, it was thought to be limited to the respiratory system; however, we now recognize that COVID-19 also affects several other organs, including the nervous system. Two similar human coronaviruses (CoV) that cause severe acute respiratory syndrome (SARS-CoV-1) and Middle East respiratory syndrome (MERS-CoV) are also known to cause disease in the nervous system. The neurological manifestations of SARS-CoV-2 infection are growing rapidly, as evidenced by several reports. There are several mechanisms responsible for such manifestations in the nervous system. For instance, post-infectious immune-mediated processes, direct virus infection of the central nervous system (CNS), and virus-induced hyperinflammatory and hypercoagulable states are commonly involved. Guillain-Barré syndrome (GBS) and its variants, dysfunction of taste and smell, and muscle injury are numerous examples of COVID-19 PNS (peripheral nervous system) disease. Likewise, hemorrhagic and ischemic stroke, encephalitis, meningitis, encephalopathy acute disseminated encephalomyelitis, endothelialitis, and venous sinus thrombosis are some instances of COVID-19 CNS disease. Due to multifactorial and complicated pathogenic mechanisms, COVID-19 poses a large-scale threat to the whole nervous system. A complete understanding of SARS-CoV-2 neurological impairments is still lacking, but our knowledge base is rapidly expanding. Therefore, we anticipate that this comprehensive review will provide valuable insights and facilitate the work of neuroscientists in unfolding different neurological dimensions of COVID-19 and other CoV associated abnormalities.
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http://dx.doi.org/10.1007/s12031-020-01767-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814864PMC
January 2021

Induction of Caspase-Mediated Apoptosis in HepG2 Liver Carcinoma Cells Using Mutagen-Antioxidant Conjugated Self-Assembled Novel Carbazole Nanoparticles and In Silico Modeling Studies.

ACS Omega 2021 Jan 21;6(1):265-277. Epub 2020 Dec 21.

Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Science, University of KwaZulu-Natal, Durban 4041, South Africa.

In this study, novel self-assembled carbazole-thiooctanoic acid nanoparticles (CTNs) were synthesized from amino carbazole (a mutagen) and thiooctanoic acid (an antioxidant). The nanoparticles were characterized using hyperspectral techniques. Then, the antiproliferative potential of CTNs was determined in HepG2 liver carcinoma cells. This study employed a solvent-antisolvent interaction method to synthesize a spherical CTN of size less than 50 nm. Moreover, CT was subsequently capped to gold nanoparticles (AuNPs) in the additional comparative studies. The CT derivative was synthesized from carbazole and lipoic acid by the amide bond formation reaction using a coupling agent. Furthermore, it was characterized using infrared (IR), H nuclear magnetic resonance, dynamic light scattering (DLS), and transmission electron microscopy techniques. The CT-capped gold nanoparticles (CTAuNPs) were prepared from CT, chloroauric acid, and NaBH. The CTAuNPs were characterized using ultraviolet-visible, high-resolution TEM, DLS, and Fourier transform IR techniques. The cytotoxicity and apoptosis-inducing ability of both nanoparticles were determined in HepG2 cells. The results demonstrate that CTNs exhibit antiproliferative activity in the cancerous HepG2 cells. Moreover, molecular docking and molecular dynamics studies were conducted to explore the therapeutic potential of CT against human EGFR suppressor protein to gain more insights into the binding mode of the CT, which may show a significant role in anticancer therapy.
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http://dx.doi.org/10.1021/acsomega.0c04461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7807466PMC
January 2021

Targeting eosinophils in respiratory diseases: Biological axis, emerging therapeutics and treatment modalities.

Life Sci 2021 Feb 2;267:118973. Epub 2021 Jan 2.

Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, NSW 2007, Australia; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute (HMRI), University of Newcastle, New Lambton Heights, Newcastle, NSW 2305, Australia; School of Pharmaceutical Sciences, Shoolini University, Solan, Himachal Pradesh 173229, India. Electronic address:

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.
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http://dx.doi.org/10.1016/j.lfs.2020.118973DOI Listing
February 2021

Nanosuspensions - An Update on Recent Patents, Methods of Preparation, and Evaluation Parameters.

Recent Pat Nanotechnol 2020 Dec 23. Epub 2020 Dec 23.

Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak. India.

Background: Nanosuspensions are colloidal systems consisting of pure drug and stabilizers, without matrix or lyophilized into a solid matrix. Nanosuspensions improve the solubility of the drug both in the aqueous and organic phases. Nanosuspensions are also known as brick dust molecules, as they increase the dissolution of a system and improve absorption.

Methods: Extensive information related to nanosuspensions and its associated patents were collected using PubMed and Google Scholar.

Results: Over the last decade nanosuspensions have attracted tremendous interest in pharmaceutical research. It provides unique features including, improved solubility, high drug loading capacity, and passive targeting. These particles are costeffective, simple, and have lesser side effects with minimal dose requirements. However, the stability of nanosuspensions still warrants attention.

Conclusion: Nanosuspensions plays a vital role in handling the numerous drug entities with difficult physico-chemical characteristics such as solubility and can further aid with a range of routes that include nasal, transdermal, occular, parenteral, pulmonary etc. This review highlights the relevance of nanosuspensions in achieving safe, effective and targeted drug delivery.
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http://dx.doi.org/10.2174/1872210514666201224103010DOI Listing
December 2020

Opening eyes to therapeutic perspectives of bioactive polyphenols and their nanoformulations against diabetic neuropathy and related complications.

Expert Opin Drug Deliv 2021 04 27;18(4):427-448. Epub 2020 Dec 27.

Department of Pharmaceutics, JSS College of Pharmacy, JSS Academy of Higher Education & Research, Ooty, Nilgiris, Tamil Nadu, India.

: Diabetic neuropathy (DN) is one of the major complications arising from hyperglycaemia in diabetic patients. In recent years polyphenols present in plants have gained attention to treat DN. The main advantages associated with them are their action via different molecular pathways to manage DN and their safety. However, they failed to gain clinical attention due to challenges associated with their formulation development such as lipophilicity,poor bioavailability, rapid systemic elimination, and enzymatic degradation.: This article includes different polyphenols that have shown their potential against DN in preclinical studies and the research carried out towards development of their nanoformulations in order to overcome aforementioned issues.: In this review various polyphenol based nanoformulations such as nanospheres, self-nanoemulsifying drug delivery systems, niosomes, electrospun nanofibers, metallic nanoparticles explored exclusively to treat DN are discussed. However, the literature available related to polyphenol based nanoformulations to treat DN is limited. Moreover, these experiments are limited to preclinical studies. Hence, more focus is required towards  development of nanoformulations using simple and single step process as well as inexpensive and non-toxic excipients so that a stable, scalable, reproducible and non-toxic formulation could be achieved and clinical trials could be initiated.
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http://dx.doi.org/10.1080/17425247.2021.1846517DOI Listing
April 2021

Interferon therapy for preventing COPD exacerbations.

EXCLI J 2020 4;19:1477-1480. Epub 2020 Nov 4.

Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, NSW 2007, Australia.

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http://dx.doi.org/10.17179/excli2020-2997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726488PMC
November 2020

Advanced drug delivery systems can assist in targeting coronavirus disease (COVID-19): A hypothesis.

Med Hypotheses 2020 Nov 10;144:110254. Epub 2020 Sep 10.

Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Ultimo, NSW 2007, Australia; Priority Research Centre for Healthy Lungs, Hunter Medical Research Institute (HMRI) & School of Biomedical Sciences and Pharmacy, The University of Newcastle (UoN), Callaghan, NSW 2308, Australia; School of Pharmaceutical Sciences, Shoolini University, Bajhol, Sultanpur, Solan, Himachal Pradesh 173 229, India. Electronic address:

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.
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http://dx.doi.org/10.1016/j.mehy.2020.110254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7481067PMC
November 2020

Anti-inflammatory and anticancer activities of Naringenin-loaded liquid crystalline nanoparticles in vitro.

J Food Biochem 2021 01 29;45(1):e13572. Epub 2020 Nov 29.

Discipline of Pharmacy, Graduate School of Health, University of Technology Sydney, Sydney, NSW, Australia.

In this study, we had developed Naringenin-loaded liquid crystalline nanoparticles (LCNs) and investigated the anti-inflammatory and anticancer activities of Naringenin-LCNs against human airway epithelium-derived basal cells (BCi-NS1.1) and human lung epithelial carcinoma (A549) cell lines, respectively. The anti-inflammatory potential of Naringenin-LCNs evaluated by qPCR revealed a decreased expression of IL-6, IL-8, IL-1β, and TNF-α in lipopolysaccharide-induced BCi-NS1.1 cells. The activity of LCNs was comparable to the positive control drug Fluticasone propionate (10 nM). The anticancer activity was studied by evaluating the antiproliferative (MTT and trypan blue assays), antimigratory (scratch wound healing assay, modified Boyden chamber assay, and immunoblot), and anticolony formation activity in A549 cells. Naringenin LCNs showed promising antiproliferative, antimigratory, and anticolony formation activities in A549 cells, in vitro. Therefore, based on our observations and results, we conclude that Naringenin-LCNs may be employed as a potential therapy-based intervention to ameliorate airway inflammation and to inhibit the progression of lung cancer. PRACTICAL APPLICATIONS: Naringenin was encapsulated into liquid crystalline nanoparticles, thus, attributing to their sustained-release nature. In addition, Naringenin-loaded LCNs efficiently reduced the levels of pro-inflammatory markers, namely, IL-1β, IL-6, TNF-α, and IL-8. In addition, the Naringenin-loaded LCNs also possess potent anticancer activity, when tested in the A549 cell line, as revealed by the inhibition of proliferation and migration of cells. They also attenuated colony formation and induced apoptosis in the A549 cells. The findings from our study could form the basis for future research that may be translated into an in vivo model to validate the possible therapeutic alternative for lung cancer using Naringenin-loaded LCNs. In addition, the applications of Naringenin-loaded LCNs as an intervention would be of great interest to biological, formulation and respiratory scientists and clinicians.
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http://dx.doi.org/10.1111/jfbc.13572DOI Listing
January 2021

Nanocarriers for treatment of dermatological diseases: Principle, perspective and practices.

Eur J Pharmacol 2021 Jan 28;890:173691. Epub 2020 Oct 28.

School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, 144411, Punjab, India.

Skin diseases are the fourth leading non-fatal skin conditions that act as a burden and affect the world economy globally. This condition affects the quality of a patient's life and has a pronounced impact on both their physical and mental state. Treatment of these skin conditions with conventional approaches shows a lack of efficacy, long treatment duration, recurrence of conditions, systemic side effects, etc., due to improper drug delivery. However, these pitfalls can be overcome with the applications of nanomedicine-based approaches that provide efficient site-specific drug delivery at the target site. These nanomedicine-based strategies are evolved as potential treatment opportunities in the form of nanocarriers such as polymeric and lipidic nanocarriers, nanoemulsions along with emerging others viz. carbon nanotubes for dermatological treatment. The current review focuses on challenges faced by the existing conventional treatments along with the topical therapeutic perspective of nanocarriers in treating various skin diseases. A total of 213 articles have been reviewed and the application of different nanocarriers in treating various skin diseases has been explained in detail through case studies of previously published research works. The toxicity related aspects of nanocarriers are also discussed.
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http://dx.doi.org/10.1016/j.ejphar.2020.173691DOI Listing
January 2021

Antiproliferative effects of boswellic acid-loaded chitosan nanoparticles on human lung cancer cell line A549.

Future Med Chem 2020 11 30;12(22):2019-2034. Epub 2020 Oct 30.

Faculty of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, 124001, India.

In the present study boswellic acids-loaded chitosan nanoparticles were synthesized using ionic gelation technique. The influence of independent variables were studied and optimized on dependent variables using central composite design. The designed nanoparticles were observed spherical in shape with an average size of 67.5-187.2 nm and have also shown an excellent entrapment efficiency (80.06 ± 0.48). The cytotoxicity assay revealed enhanced cytotoxicity for drug-loaded nanoparticles in contrast to the free drug having an IC value of 17.29 and 29.59 μM, respectively. Flow cytometry confirmed that treatment of cells with 40 μg/ml had arrested 22.75 ± 0.3% at SubG phase of the cell cycle when compared with untreated A459 cells. The observed results justified the boswellic acids-loaded chitosan nanoparticles were effective due to greater cellular uptake, sustained intercellular drug retention and enhanced antiproliferative effect by inducing apoptosis.
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http://dx.doi.org/10.4155/fmc-2020-0083DOI Listing
November 2020

Solid lipid nanoparticles containing anti-tubercular drugs attenuate the Mycobacterium marinum infection.

Tuberculosis (Edinb) 2020 12 10;125:102008. Epub 2020 Oct 10.

Department of Pharmaceutical Sciences, Maharshi Dayanand University, Rohtak, Haryana, India. Electronic address:

The present study aimed to formulate anti-tubercular drugs (Rifampicin, Isoniazid and Pyrazinamide) loaded solid lipid nanoparticles (ATDs-SLNs) using microemulsion technique for oral administration. Central composite designed (CCD) was applied to study the effect of stearic acid (X), Compritol® 888 ATO (X) and equal ratio of poloxamer 188: sodium taurocholate (% w/w) (X) on particle size, zeta potential and entrapment efficiency. The optimised formulation (SLN) was found to be spherical in shape with mean particle size 187.9 ± 10.73 nm and zeta potential -47.4 mV. The maximum percentage entrapment of RIF, INH and PYZ in the optimised formulation was found to be 86.40 ± 0.274, 83.84 ± 0.269 and 81.43 ± 0.576, respectively. The in-vitro drug release study demonstrated that the release of drug from SLNs was slow in comparison to marketed formulation and pure ATDs. Cytotoxicity of the ATDs-SLNs was studied on murine macrophage cell line (RAW 264.7) using modified MTT assay demonstrated two folds growth inhibition of M. marinum as compared to standard antitubercular drugs. Overall, the developed SLNs may be considered as a promising anti-mycobacterial nano-drug, providing a new direction to the tuberculosis clinics.
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http://dx.doi.org/10.1016/j.tube.2020.102008DOI Listing
December 2020

COVID-19: Underpinning Research for Detection, Therapeutics, and Vaccines Development.

Pharm Nanotechnol 2020 ;8(4):323-353

School of Pharmacy and Pharmaceutical Science, Ulster University, Coleraine, County Londonderry, Northern Ireland, United Kingdom.

Background: The newly emerged coronavirus SARS-CoV-2, first reported in December 2019, has infected about five and a half million people globally and resulted in nearly 9063264 deaths until the 24th of June 2020. Nevertheless, the highly contagious virus has instigated an unimaginably rapid response from scientific and medical communities.

Objectives: Pioneering research on molecular mechanisms underlying the viral transmission, molecular pathogenicity, and potential treatments will be highlighted in this review. The development of antiviral drugs specific to SARS-CoV-2 is a complicated and tedious process. To accelerate scientific discoveries and advancement, researchers are consolidating available data from associated coronaviruses into a single pipeline, which can be readily made available to vaccine developers.

Methods: In order to find studies evaluating the COVID-19 virus epidemiology, repurposed drugs and potential vaccines, web searches and bibliographical bases have been used with keywords that matches the content of this review.

Results: The published results of SARS-CoV-2 structures and interactomics have been used to identify potential therapeutic candidates. We illustrate recent publications on SARS-CoV-2, concerning its molecular, epidemiological, and clinical characteristics, and focus on innovative diagnostics technologies in the production pipeline. This objective of this review is to enhance the comprehension of the unique characteristics of SARS-CoV-2 and strengthen future control measures.

Lay Summary: An innovative analysis is evaluating the nature of the COVID-19 pandemic. The aim is to increase knowledge of possible viral detection methods, which highlights several new technology limitations and advantages. We have assessed some drugs currently for patients (Lopinavir, Ritonavir, Anakinra and Interferon beta 1a), as the feasibility of COVID-19 specific antivirals is not presently known. The study explores the race toward vaccine development and highlights some significant trials and candidates in various clinical phases. This research addresses critical knowledge gaps by identifying repurposed drugs currently under clinical trials. Findings will be fed back rapidly to the researchers interested in COVID 19 and support the evidence and potential of possible therapeutics and small molecules with their mode of action.
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http://dx.doi.org/10.2174/2211738508999200817163335DOI Listing
October 2020
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