Displaying publications 41 - 59 of 59 in total

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  1. Monotherapy of RAAS blockers and mobilization of aldosterone: A mechanistic perspective study in kidney disease
    Gupta G, Dahiya R, Singh Y, Mishra A, Verma A, Gothwal SK, et al.
    Chem Biol Interact, 2020 Feb 01;317:108975.
    PMID: 32032593 DOI: 10.1016/j.cbi.2020.108975
    In patients with acute kidney injury progressively converting into chronic kidney disease (CKD), proteinuria and high blood pressure predict progression to end-stage renal disease (ESRD). Although, Renin-angiotensin-aldosterone system (RAAS) regulates blood pressure and kidney disease through both direct and indirect mechanisms. RAAS blockers that act at the level of angiotensin or lower in the cascade can cause compensatory increases in the plasma renin and angiotensin II level. Here, in this review article, we are exploring the evidence-based on RAAS blockade action releases of aldosterone and hypothesizing the molecular mechanism for converting the acute kidney injury into chronic kidney disease to end-stage renal disease.
  2. Nanocarriers: more than tour de force for thymoquinone
    Rathore C, Rathbone MJ, Chellappan DK, Tambuwala MM, Pinto TJA, Dureja H, et al.
    Expert Opin Drug Deliv, 2020 04;17(4):479-494.
    PMID: 32077770 DOI: 10.1080/17425247.2020.1730808
    Introduction: Thymoquinone (TQ), 2-isopropyl-5-methylbenzo-1, 4-quinone, the main active constituent of Nigella sativa (NS) plant, has been proven to be of great therapeutic aid in various in vitro and in vivo conditions. Despite the promising therapeutic activities of TQ, this molecule is not yet in the clinical trials, restricted by its poor biopharmaceutical properties including photo-instability.Area covered: This review compiles the different types of polymeric and lipidic nanocarriers (NCs), encapsulating TQ for their improved oral bioavailability, and augmented in vitro and in vivo efficacy, evidenced on various pathologies. Furthermore, we provide a comprehensive overview of TQ in relation to its encapsulation approaches advancing the delivery and improving the efficacy of TQ.Expert opinion: TQ was first identified in the essential oil of Nigella sativa L. black seed. TQ has not been used in formulations because it is a highly hydrophobic drug having poor aqueous solubility. To deal with the poor physicochemical problems associated with TQ, various NCs encapsulating TQ have been tried in the past. Nevertheless, these NCs could be impending in bringing forth this potential molecule to clinical reality. This will also be beneficial for a large research community including pharmaceutical & biological sciences and translational researchers.
  3. Nanosuspensions - An Update on Recent Patents, Methods of Preparation, and Evaluation Parameters
    Khanuja HK, Awasthi R, Mehta M, Satija S, Aljabali AAA, Tambuwala MM, et al.
    Recent Pat Nanotechnol, 2021;15(4):351-366.
    PMID: 33357187 DOI: 10.2174/1872210514666201224103010
    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 Pub Med 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 cost-effective, simple, and have lesser side effects with minimal dose requirements. However, the stability of nanosuspensions still warrants attention.

    CONCLUSION: Nanosuspensions play 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, ocular, parenteral, pulmonary etc. This review highlights the relevance of nanosuspensions in achieving safe, effective and targeted drug delivery.

  4. Nucleic Acid Aptamers as a Potential Nucleus Targeted Drug Delivery System
    Shrivastava G, Bakshi HA, Aljabali AA, Mishra V, Hakkim FL, Charbe NB, et al.
    Curr Drug Deliv, 2020;17(2):101-111.
    PMID: 31906837 DOI: 10.2174/1567201817666200106104332
    BACKGROUND: Nucleus targeted drug delivery provides several opportunities for the treatment of fatal diseases such as cancer. However, the complex nucleocytoplasmic barriers pose significant challenges for delivering a drug directly and efficiently into the nucleus. Aptamers representing singlestranded DNA and RNA qualify as next-generation highly advanced and personalized medicinal agents that successfully inhibit the expression of certain proteins; possess extraordinary gene-expression for manoeuvring the diseased cell's fate with negligible toxicity. In addition, the precisely directed aptamers to the site of action present a tremendous potential to reach the nucleus by escaping the ensuing barriers to exhibit a better drug activity and gene expression.

    OBJECTIVE: This review epigrammatically highlights the significance of targeted drug delivery and presents a comprehensive description of the principal barriers faced by the nucleus targeted drug delivery paradigm and ensuing complexities thereof. Eventually, the progress of nucleus targeting with nucleic acid aptamers and success achieved so far have also been reviewed.

    METHODS: Systematic literature search was conducted of research published to date in the field of nucleic acid aptamers.

    CONCLUSION: The review specifically points out the contribution of individual aptamers as the nucleustargeting agent rather than aptamers in conjugated form.

  5. Overview of key molecular and pharmacological targets for diabetes and associated diseases
    Shahcheraghi SH, Aljabali AAA, Al Zoubi MS, Mishra V, Charbe NB, Haggag YA, et al.
    Life Sci, 2021 Aug 01;278:119632.
    PMID: 34019900 DOI: 10.1016/j.lfs.2021.119632
    Diabetes epidemiological quantities are demonstrating one of the most important communities' health worries. The essential diabetic difficulties are including cardiomyopathy, nephropathy, inflammation, and retinopathy. Despite developments in glucose decreasing treatments and drugs, these diabetic complications are still ineffectively reversed or prohibited. Several signaling and molecular pathways are vital targets in the new therapies of diabetes. This review assesses the newest researches about the key molecules and signaling pathways as targets of molecular pharmacology in diabetes and diseases related to it for better treatment based on molecular sciences. The disease is not cured by current pharmacological strategies for type 2 diabetes. While several drug combinations are accessible that can efficiently modulate glycemia and mitigate long-term complications, these agents do not reverse pathogenesis, and in practice, they are not established to modify the patient's specific molecular profiling. Therapeutic companies have benefited from human genetics. Genome exploration, which is agnostic to the information that exists, has revealed tens of loci that impact glycemic modulation. The physiological report has begun to examine subtypes of diseases, illustrate heterogeneity and propose biochemical therapeutic pathways.
  6. Perfluorocarbons Therapeutics in Modern Cancer Nanotechnology for Hypoxiainduced Anti-tumor Therapy
    Satija S, Sharma P, Kaur H, Dhanjal DS, Chopra RS, Khurana N, et al.
    Curr Pharm Des, 2021;27(43):4376-4387.
    PMID: 34459378 DOI: 10.2174/1381612827666210830100907
    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.
  7. Pharmaceutical Aspects of Green Synthesized Silver Nanoparticles: A Boon to Cancer Treatment
    Mishra V, Nayak P, Singh M, Tambuwala MM, Aljabali AA, Chellappan DK, et al.
    Anticancer Agents Med Chem, 2021;21(12):1490-1509.
    PMID: 32951580 DOI: 10.2174/1871520620666200918111024
    BACKGROUND: Silver nanoparticles (AgNPs) are among the most investigated nanostructures in recent years, which exhibit more challenging and promising qualities in different biomedical applications. The AgNPs synthesized by the green approach provide potential healthcare benefits over chemical approaches, including improvement of tissue restoration, drug delivery, diagnosis, being environmentally friendly, and a boon to cancer treatment.

    OBJECTIVE: In the current scenario, the development of safe and effective drug delivery systems is the utmost concern of formulation development scientists as well as clinicians.

    METHODS: Google, Web of Science, and PubMed portals have been searched for potentially relevant literature to get the latest developments and updated information related to different aspects of green synthesized AgNPs along with their biomedical applications, especially in the treatment of different types of cancers.

    RESULTS: The present review highlights the latest published research regarding the different green approaches for the synthesis of AgNPs, their characterization techniques as well as various biomedical applications, particularly in cancer treatment. In this context, environment-friendly AgNPs are proving themselves as better candidates in terms of size, drug loading and release efficiency, targeting efficiency, minimal drug-associated side effects, pharmacokinetic profiling, and biocompatibility issues.

    CONCLUSION: With continuous efforts by multidisciplinary team approaches, nanotechnology-based AgNPs will shed new light on diagnostics and therapeutics in various disease treatments. However, the toxicity issues of AgNPs need greater attention as unanticipated toxic effects must be ruled out for their diversified applications.

  8. Fulltext Plants derived therapeutic strategies targeting chronic respiratory diseases: Chemical and immunological perspective
    Prasher P, Sharma M, Mehta M, Paudel KR, Satija S, Chellappan DK, et al.
    Chem Biol Interact, 2020 Jul 01;325:109125.
    PMID: 32376238 DOI: 10.1016/j.cbi.2020.109125
    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.
  9. Probing 3CL protease: Rationally designed chemical moieties for COVID-19
    Sharma M, Prasher P, Mehta M, Zacconi FC, Singh Y, Kapoor DN, et al.
    Drug Dev Res, 2020 Jul 30.
    PMID: 32729640 DOI: 10.1002/ddr.21724
  10. Recent Advances in Self-Assembled Nanoparticles for Drug Delivery
    Varma LT, Singh N, Gorain B, Choudhury H, Tambuwala MM, Kesharwani P, et al.
    Curr Drug Deliv, 2020;17(4):279-291.
    PMID: 32039683 DOI: 10.2174/1567201817666200210122340
    The collection of different bulk materials forms the nanoparticles, where the properties of the nanoparticle are solely different from the individual components before being ensembled. Selfassembled nanoparticles are basically a group of complex functional units that are formed by gathering the individual bulk components of the system. It includes micelles, polymeric nanoparticle, carbon nanotubes, liposomes and niosomes, etc. This self-assembly has progressively heightened interest to control the final complex structure of the nanoparticle and its associated properties. The main challenge of formulating self-assembled nanoparticle is to improve the delivery system, bioavailability, enhance circulation time, confer molecular targeting, controlled release, protection of the incorporated drug from external environment and also serve as nanocarriers for macromolecules. Ultimately, these self-assembled nanoparticles facilitate to overcome the physiological barriers in vivo. Self-assembly is an equilibrium process where both individual and assembled components are subsisting in equilibrium. It is a bottom up approach in which molecules are assembled spontaneously, non-covalently into a stable and welldefined structure. There are different approaches that have been adopted in fabrication of self-assembled nanoparticles by the researchers. The current review is enriched with strategies for nanoparticle selfassembly, associated properties, and its application in therapy.
  11. Role of the Serine/Threonine Kinase 11 (STK11) or Liver Kinase B1 (LKB1) Gene in Peutz-Jeghers Syndrome
    Altamish M, Dahiya R, Singh AK, Mishra A, Aljabali AAA, Satija S, et al.
    Crit Rev Eukaryot Gene Expr, 2020;30(3):245-252.
    PMID: 32749111 DOI: 10.1615/CritRevEukaryotGeneExpr.2020033451
    Peutz-Jeghers syndrome (PJS) is a well-described inherited syndrome, characterized by the development of gastrointestinal polyps and characteristic mucocutaneous freckling. PJS is an autosomal prevailing disease, due to genetic mutation on chromosome 19p, manifested by restricted mucocutaneous melanosis in association with gastrointestinal (GI) polyposis. The gene for PJS has recently been shown to be a serine/threonine kinase, known as LKB1 or STK11, which maps to chromosome subband 19p13.3. This gene has a putative coding region of 1302 bp, divided into nine exons, and acts as a tumor suppressor in the hamartomatous polyps of PJS patients and in the other neoplasms that develop in PJS patients. It is probable that these neoplasms develop from hamartomas, but it remains possible that the LKB1 or STK11 locus plays a role in a different genetic pathway of tumor growth in the cancers of PJS patients. This article focuses on the role of LKB1 or STK11 gene expression in PJS and related cancers.
  12. Fulltext Self-nanoemulsifying drug delivery system (SNEDDS) mediated improved oral bioavailability of thymoquinone: optimization, characterization, pharmacokinetic, and hepatotoxicity studies
    Rathore C, Hemrajani C, Sharma AK, Gupta PK, Jha NK, Aljabali AAA, et al.
    Drug Deliv Transl Res, 2023 Jan;13(1):292-307.
    PMID: 35831776 DOI: 10.1007/s13346-022-01193-8
    Thymoquinone (TQ) is an antioxidant, anti-inflammatory, and hepatoprotective compound obtained from the black seed oil of Nigella sativa. However, high hydrophobicity, instability at higher pH levels, photosensitivity, and low oral bioavailability hinder its delivery to the target tissues. A self-nanoemulsifying drug delivery system (SNEDDS) was fabricated using the microemulsification technique to address these issues. Its physicochemical properties, thermodynamic stability studies, drug release kinetics, in vivo pharmacokinetics, and hepatoprotective activity were evaluated. The droplet size was in the nano-range (
  13. Small interfering RNA for cancer treatment: overcoming hurdles in delivery
    Charbe NB, Amnerkar ND, Ramesh B, Tambuwala MM, Bakshi HA, Aljabali AAA, et al.
    Acta Pharm Sin B, 2020 Nov;10(11):2075-2109.
    PMID: 33304780 DOI: 10.1016/j.apsb.2020.10.005
    In many ways, cancer cells are different from healthy cells. A lot of tactical nano-based drug delivery systems are based on the difference between cancer and healthy cells. Currently, nanotechnology-based delivery systems are the most promising tool to deliver DNA-based products to cancer cells. This review aims to highlight the latest development in the lipids and polymeric nanocarrier for siRNA delivery to the cancer cells. It also provides the necessary information about siRNA development and its mechanism of action. Overall, this review gives us a clear picture of lipid and polymer-based drug delivery systems, which in the future could form the base to translate the basic siRNA biology into siRNA-based cancer therapies.
  14. Fulltext Targeting LIN28: a new hope in prostate cancer theranostics
    Shrivastava G, Aljabali AA, Shahcheraghi SH, Lotfi M, Shastri MD, Shukla SD, et al.
    Future Oncol, 2021 Oct;17(29):3873-3880.
    PMID: 34263659 DOI: 10.2217/fon-2021-0247
    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.
  15. Targeting eosinophils in respiratory diseases: Biological axis, emerging therapeutics and treatment modalities
    Lee LY, Hew GSY, Mehta M, Shukla SD, Satija S, Khurana N, et al.
    Life Sci, 2021 Feb 15;267:118973.
    PMID: 33400932 DOI: 10.1016/j.lfs.2020.118973
    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.
  16. Targeting neutrophils using novel drug delivery systems in chronic respiratory diseases
    Chellappan DK, Yee LW, Xuan KY, Kunalan K, Rou LC, Jean LS, et al.
    Drug Dev Res, 2020 06;81(4):419-436.
    PMID: 32048757 DOI: 10.1002/ddr.21648
    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.
  17. The potential of siRNA based drug delivery in respiratory disorders: Recent advances and progress
    Dua K, Wadhwa R, Singhvi G, Rapalli V, Shukla SD, Shastri MD, et al.
    Drug Dev Res, 2019 09;80(6):714-730.
    PMID: 31691339 DOI: 10.1002/ddr.21571
    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.
  18. Fulltext The viral capsid as novel nanomaterials for drug delivery
    Aljabali AA, Hassan SS, Pabari RM, Shahcheraghi SH, Mishra V, Charbe NB, et al.
    Future Sci OA, 2021 Oct;7(9):FSO744.
    PMID: 34737885 DOI: 10.2144/fsoa-2021-0031
    The purpose of this review is to highlight recent scientific developments and provide an overview of virus self-assembly and viral particle dynamics. Viruses are organized supramolecular structures with distinct yet related features and functions. Plant viruses are extensively used in biotechnology, and virus-like particulate matter is generated by genetic modification. Both provide a material-based means for selective distribution and delivery of drug molecules. Through surface engineering of their capsids, virus-derived nanomaterials facilitate various potential applications for selective drug delivery. Viruses have significant implications in chemotherapy, gene transfer, vaccine production, immunotherapy and molecular imaging.
  19. Vitamin D, Calbindin, and calcium signaling: Unraveling the Alzheimer's connection
    Acharya M, Singh N, Gupta G, Tambuwala MM, Aljabali AAA, Chellappan DK, et al.
    Cell Signal, 2024 Apr;116:111043.
    PMID: 38211841 DOI: 10.1016/j.cellsig.2024.111043
    Calcium is a ubiquitous second messenger that is indispensable in regulating neurotransmission and memory formation. A precise intracellular calcium level is achieved through the concerted action of calcium channels, and calcium exerts its effect by binding to an array of calcium-binding proteins, including calmodulin (CAM), calcium-calmodulin complex-dependent protein kinase-II (CAMK-II), calbindin (CAL), and calcineurin (CAN). Calbindin orchestrates a plethora of signaling events that regulate synaptic transmission and depolarizing signals. Vitamin D, an endogenous fat-soluble metabolite, is synthesized in the skin upon exposure to ultraviolet B radiation. It modulates calcium signaling by increasing the expression of the calcium-sensing receptor (CaSR), stimulating phospholipase C activity, and regulating the expression of calcium channels such as TRPV6. Vitamin D also modulates the activity of calcium-binding proteins, including CAM and calbindin, and increases their expression. Calbindin, a high-affinity calcium-binding protein, is involved in calcium buffering and transport in neurons. It has been shown to inhibit apoptosis and caspase-3 activity stimulated by presenilin 1 and 2 in AD. Whereas CAM, another calcium-binding protein, is implicated in regulating neurotransmitter release and memory formation by phosphorylating CAN, CAMK-II, and other calcium-regulated proteins. CAMK-II and CAN regulate actin-induced spine shape changes, which are further modulated by CAM. Low levels of both calbindin and vitamin D are attributed to the pathology of Alzheimer's disease. Further research on vitamin D via calbindin-CAMK-II signaling may provide newer insights, revealing novel therapeutic targets and strategies for treatment.
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