Department of Pharmacy

Permanent URI for this collectionhttp://localhost:4000/handle/123456789/1931

Browse

Has files: NoSubject: search.filters.subject.Cancer

Search Results

Now showing 1 - 10 of 35
  • No Thumbnail Available
    Item
    Lineage of lipid-based endosomal escape in cytosolic delivery to cancer: insight into an unprecedented approach
    (Elsevier, 2025-12) Jain, Ankit
    Endosomal sequestration of lipid-based systems constitutes a significant limitation that undermines the efficient intracellular delivery of therapeutics in cancer treatment. Upon administration, the intracellular fate of drug or gene constructs within lipid-based delivery systems is influenced by various factors, including p-glycoprotein-mediated efflux and lysosomal degradation, which impede sufficient therapeutic agents from reaching their intended targets. This review exhaustively discusses lipids (properties of lipids and role of pKa) and various lipid-based delivery systems facilitating the endosomal escape for cancer treatment. All aspects, such as endosomal sequestration, methods to promote endosomal escape, a mechanistic overview of endosomal escape, detection of endosomal escape, the application potential of lipid-based systems for cancer treatment, and safety of lipid-based systems, were covered in this manuscript. Existing reviews on endosomal escape have accounted for the various mechanisms,. Still, this review paper also furnishes the role of pKa and applications of molecular dynamic simulation in lipid-based drug delivery, and safety concernsof lipid-based nanosystems. This review discussed the influence of material properties on the endosomal escape of therapeutic agents.
  • No Thumbnail Available
    Item
    Design, synthesis, and biological evaluation of novel quinazolin-4(3h)-one-based histone deacetylase 6 (hdac6) inhibitors for anticancer activity
    (MDPI, 2023-07) Murugesan, Sankaranarayanan
    A series of novel quinazoline-4-(3H)-one derivatives were designed and synthesized as histone deacetylase 6 (HDAC6) inhibitors based on novel quinazoline-4-(3H)-one as the cap group and benzhydroxamic acid as the linker and metal-binding group. A total of 19 novel quinazoline-4-(3H)-one analogues (5a–5s) were obtained. The structures of the target compounds were characterized using 1H-NMR, 13C-NMR, LC–MS, and elemental analyses. Characterized compounds were screened for inhibition against HDAC8 class I, HDAC4 class IIa, and HDAC6 class IIb. Among the compounds tested, 5b proved to be the most potent and selective inhibitor of HDAC6 with an IC50 value 150 nM. Some of these compounds showed potent antiproliferative activity in several tumor cell lines (HCT116, MCF7, and B16). Amongst all the compounds tested for their anticancer effect against cancer cell lines, 5c emerged to be most active against the MCF-7 line with an IC50 of 13.7 μM; it exhibited cell-cycle arrest in the G2 phase, as well as promoted apoptosis. Additionally, we noted a significant reduction in the colony-forming capability of cancer cells in the presence of 5c. At the intracellular level, selective inhibition of HDAC6 was enumerated by monitoring the acetylation of α-tubulin with a limited effect on acetyl-H3. Importantly, the obtained results suggested a potent effect of 5c at sub-micromolar concentrations as compared to the other molecules as HDAC6 inhibitors in vitro.
  • No Thumbnail Available
    Item
    Pharmacoinformatics-based prediction of checkpoint kinase-1 inhibitors from momordica charantia linn. for cancer
    (Elsevier, 2025-04) Murugesan, Sankaranarayanan
    Checkpoint kinase 1 (Chk-1), a serine/threonine kinase family protein, is an emerging target in cancer research owing to its crucial role in cell cycle arrest. Therefore, we aimed to predict potential Chk-1 inhibitors from Momordica charantia Linn., using high-throughput molecular docking. We used a graph theoretical network approach to determine the target protein, Chk-1. Among 86 compounds identified from M. charantia L., five molecules such as α-spinasterol (-9.7 kcal × mol−1), stigmasterol (-9.6 kcal × mol−1), stigmasta-7,22,25-trienol (-9.5 kcal × mol−1), campesterol (-9.5 kcal × mol−1), and stigmasta-7,25-dien-3beta-ol (-9.5 kcal × mol−1) and standard drug CCT245737 (-8.3 kcal × mol-1) displayed highest binding affinity with Chk-1. Besides, pharmacokinetic studies have demonstrated the non-toxic and drug-like properties of these compounds. Furthermore, molecular dynamics (MD) simulation studies confirmed the strong intermolecular interactions and stability of the compounds with Chk-1. The estimation of binding free-energy derived from molecular docking was fully recognized by the Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) produced from the MD simulation paths. Altogether, these five compounds may serve as effective inhibitors of Chk-1, thereby could be used to develop new medications for cancer treatment.
  • No Thumbnail Available
    Item
    Downregulation of microRNA-29b in cancer and fibrosis: molecular insights and clinical implications
    (Elsevier, 2024-11) Chitkara, Deepak
    MicroRNA-29b (miR-29b) is known for its therapeutic potential as an antifibrotic and anticancer agent. In fibrotic conditions, miR-29b inhibits fibrogenesis by downregulating crucial regulators such as collagens, extracellular matrix proteins and the transforming growth factor-β pathway. Similarly, in cancer, it acts as a tumor suppressor by downregulating various oncogenes and signaling pathways involved in cancer progression, such as Wnt–β-catenin, p38–mitogen-activated protein kinase and nuclear factor-κB. However, the upregulation of these pathways suppresses miR-29b, contributing to fibrosis and cancer development. Preclinical research and clinical trials have shown that delivering exogenous miR-29b mimics can restore its expression, attenuating tumorigenesis and fibrogenesis. This review discusses miR-29b’s potential and its possible therapeutic development for cancer and fibrotic disorders.
  • No Thumbnail Available
    Item
    Liposomal delivery system
    (Springer, 2022-03) Jain, Ankit
    Liposomes are biodegradable and biocompatible lipid bilayer vesicles that are employed as potential carriers for the delivery of drugs to the desired site. It is used for the delivery of both hydrophobic and hydrophilic drugs. Because of the variability in composition and structural properties, liposomes are widely used in biomedical applications. Recently, multifunctional liposomes have been reported for tumor targeting. Liposomal delivery systems are modified in several ways according to their applications. Ligand-modified liposomes are used for targeted drug delivery. Stimuli-sensitive liposomes are used to obtain the trigger drug release at the site of action. Theranostic liposomal systems are used for diagnosis as well as therapeutic purposes. This chapter highlights the basics and classification of liposomes. It encompasses a detailed account of ligand targeted liposomes (such as folate, transferrin, mannose, hyaluronic acid, and asialoglycoprotein), and stimuli-sensitive liposomes (such as pH, temperature, magnetic field, hypoxia, and photo-triggered) for tumor targeting. It also includes some marketed liposomal products used for cancer treatment
  • No Thumbnail Available
    Item
    A glimpse of biomedical application potential of biodegradable polymers for anticancer drug delivery
    (Elsevier, 2022) Jain, Ankit
    The major anticancer drugs used for cancer therapy show nonspecificity, wide biodistribution, a short half-life, a low concentration in tumor tissue, and systemic toxicity. The biodegradable polymer can be used as an approach that acts as a drug carrier, offering a targeted drug delivery and increasing the drug payload to the tumor tissues and cells. It also enhances biocompatibility, provides prolonged release of the drug allowing controlled and sustained release, and minimizes systemic toxicity. This chapter focuses on targeted drug delivery through a stimuli-responsive drug carrier that releases its payload at the specified site and on demand in response to an external stimulus. It also emphasizes various applications of biodegradable polymers in breast cancer, lung cancer, colon cancer, and uterine cancer with special emphasis on theranostic applications.
  • No Thumbnail Available
    Item
    Theranostic nanocarriers for cancer applications
    (CRC Press, 2024) Jain, Ankit
    Cancer is one of the deadly diseases with serious health concerns that needed novel therapeutic solutions. For an effective and successful treatment approach, upgraded and advanced diagnostics as well as therapeutic techniques are required. Currently, research and development in this area are in great demand in nanoscience and nanotechnology. They promise to offer innovative and more effective approaches to cancer for its early diagnosis, imaging, and therapy. An emerging and growing trend in this direction is theranostics. It deals with both the diagnosis and therapeutic approach to cancers conjointly. Its prime objectives are to eliminate multi-step processes and reduce delays in cancer treatment. It offers many advantages, such as better-quality diagnosis, cancer-specific drug delivery, and minimization of toxic effects to healthy tissues. Many theranostic nanocarriers like nanoparticles, quantum dots, carbon nanotubes, nanofibers, nanoshells, liposomes, dendrimers, and micelles can be used efficiently for the effective treatment of cancer. This chapter examines several theranostic nanocarriers and their applications for effective cancer treatment.
  • No Thumbnail Available
    Item
    Navigating liver cancer: precision targeting for enhanced treatment outcomes
    (Springer, 2025-01) Jain, Ankit
    Cancer treatments such as surgery and chemotherapy have several limitations, including ineffectiveness against large or persistent tumors, high relapse rates, drug toxicity, and non-specificity of therapy. Researchers are exploring advanced strategies for treating this life-threatening disease to address these challenges. One promising approach is targeted drug delivery using prodrugs or surface modification with receptor-specific moieties for active or passive targeting. While various drug delivery systems have shown potential for reaching hepatic cells, nano-carriers offer significant size, distribution, and targetability advantages. Engineered nanocarriers can be customized to achieve effective and safe targeting of tumors by manipulating physical characteristics such as particle size or attaching receptor-specific ligands. This method is particularly advantageous in treating liver cancer by targeting specific hepatocyte receptors and enzymatic pathways for both passive and active therapeutic strategies. It highlights the epidemiology of liver cancer and provides an in-depth analysis of the various targeting approaches, including prodrugs, liposomes, magneto-liposomes, micelles, glycol-dendrimers, magnetic nanoparticles, chylomicron-based emulsion, and quantum dots surface modification with receptor-specific moieties. The insights from this review can be immensely significant for preclinical and clinical researchers working towards developing effective treatments for liver cancer. By utilizing these novel strategies, we can overcome the limitations of conventional therapies and offer better outcomes for liver cancer patients.
  • No Thumbnail Available
    Item
    An insight into risk assessment and reformulation of drug products manufactured using benzene grade carbomer: a regulatory perspective
    (Springer, 2024-07) Jindal, Anil B.
    Cancer has been an enormous pain point for patients and regulatory bodies across the globe. In Dec. 2023, the US FDA released guidance on benzene-grade carbomer formulations, which triggered pharmaceutical manufacturers to assess risk, test finished products, and reformulate drug products with benzene-grade carbomer. The immediate implementation of the stoppage of finished products with benzene-grade carbomers has threatened pharmaceutical excipients and finished product manufacturers. The gravity of this situation prompted the US Pharmacopeia to extend the deadline for discontinuation from August 1, 2025, to August 1, 2026, allowing manufacturers ample time for reformulation and regulatory compliance. There is an immediate need to understand the guidance and to learn how manufacturers should do the risk assessment and approach reformulation. This review provides an in-depth analysis of the risk assessment and reformulation processes involved in various dosage forms utilizing benzene-grade carbomer, supported by specific case studies. This review offers insights into navigating the USFDA guidelines to ensure formulation safety and compliance, thus enabling pharmaceutical practitioners to uphold the highest standards of patient care and tackle life cycle management challenges.
  • No Thumbnail Available
    Item
    Mechanism of interaction between autophagy and apoptosis in cancer
    (Springer, 2021-09) Shrivastava, Richa
    The mechanisms of two programmed cell death pathways, autophagy, and apoptosis, are extensively focused areas of research in the context of cancer. Both the catabolic pathways play a significant role in maintaining cellular as well as organismal homeostasis. Autophagy facilitates this by degradation and elimination of misfolded proteins and damaged organelles, while apoptosis induces canonical cell death in response to various stimuli. Ideally, both autophagy and apoptosis have a role in tumor suppression, as autophagy helps in eliminating the tumor cells, and apoptosis prevents their survival. However, as cancer proceeds, autophagy exhibits a dual role by enhancing cancer cell survival in response to stress conditions like hypoxia, thereby promoting chemoresistance to the tumor cells. Thus, any inadequacy in either of their levels can lead to tumor progression. A complex array of biomarkers is involved in maintaining coordination between the two by acting as either positive or negative regulators of one or both of these pathways of cell death. The resulting crosstalk between the two and its role in influencing the survival or death of malignant cells makes it quintessential, among other challenges facing chemotherapeutic treatment of cancer. In view of this, the present review aims to highlight some of the factors involved in maintaining their diaphony and stresses the importance of inhibition of cytoprotective autophagy and deletion of the intermediate pathways involved to facilitate tumor cell death. This will pave the way for future prospects in designing drug combinations facilitating the synergistic effect of autophagy and apoptosis in achieving cancer cell death.