Browsing by Author "Manjit"

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Dual targeting pH responsive chitosan nanoparticles for enhanced active cellular internalization of gemcitabine in non-small cell lung cancer
(Elsevier B.V., 2023) Krishan Kumar; Shiv Govind Rawat; Manjit; Mohini Mishra; Priya; Ajay Kumar; Ruchi Chawla
Lung cancer (LC), related with the enhanced expression of epidermal growth factor receptor (EGFR) and sialic acid binding receptors (glycan) brought about the development of EGFR and glycan receptor specific anticancer therapeutics. The current study assessed the formulation, physiochemical characterization, in vitro and in vivo effects of sialic acid (SA) and cetuximab (Cxmab) decorated chitosan nanoparticles (CSN-NPs) loaded with gemcitabine (GMC) targeted to glycan and EGFR over-expressing non-small-cell lung-cancer (NSCLC) A-549 cells. Chitosan (CSN) was conjugated with sialic acid via EDC/NHS chemistry followed by gemcitabine loaded sialic acid conjugated chitosan nanoparticles (GMC-CSN-SA-NPs) were prepared by ionic gelation method decorated with Cxmab by electrostatic interaction. In vitro cytotoxicity of NPs quantified using cell based MTT, DAPI and Annexing-V/PI apoptosis assays showed superior antiproliferative activity of targeted nanoformulations (GMC-CSN-SA-Cxmab-NPs ≫ GMC-CSN-SA-NPs, GMC-CSN-Cxmab-NPs) over non-targeted nanoformulation (GMC-CSN-NPs) against A-549 cells. In vivo pharmacokinetic study showed superior bioavailability and in vivo therapeutic efficacy investigation exhibited strongest anticancer activity of glycan and EGFR targeted NPs (GMC-CSN-SA-Cxmab-NPs). GMC-CSN-SA-Cxmab-NPs demonstrated enhanced cellular internalization and better therapeutic potential, by specifically targeting glycan and EGFR on NSCLC A-549 cells and B[a]P induced lung cancer mice model, hence it might be a good substitute for non-targeted, conventional chemotherapy. © 2023 Elsevier B.V.
In-silico exploration of Attukal Kizhangu L. compounds: Promising candidates for periodontitis treatment
(Elsevier Ltd, 2024) Pragati Dubey; Manjit; Asha Rani; Neelam Mittal; Brahmeshwar Mishra
A medicinal pteridophyte known as Attukal Kizhangu L. has been used to cure patients for centuries by administering plant parts based on conventional and common practices. Regarding its biological functions, significant use and advancement have been made. Extract of Attukal Kizhangu L. is the subject of the current study, which uses network pharmacology as its foundation. Three targeted compounds such as α-Lapachone, Dihydrochalcone, and Piperine were chosen for additional research from the 17 Phytoconstituents that were filtered out by the Coupled UPLC-HRMS study since they followed to Lipinski rule and showed no toxicity. The pharmacokinetics and physicochemical properties of these targeted compounds were analyzed by using three online web servers pkCSM, Swiss ADME, and Protox-II. This is the first in silico study to document these compound's effectiveness against the standard drug DOX in treating Periodontitis. The Swiss target prediction database was used to retrieve the targets of these compounds. DisGeNET and GeneCards were used to extract the targets of periodontitis. The top five hub genes were identified by Cytoscape utilizing the protein-protein interaction of common genes, from which two hub genes and three binding proteins of collagenase enzymes were used for further studies AA2, PGE2, PI2, TNFA, and PGP. The minimal binding energy observed in molecular docking, indicative of the optimal docking score, corresponds to the highest affinity between the protein and ligand. To corroborate the findings of the docking study, molecular dynamics (MD) simulations, and MMPBSA calculations were conducted for the complexes involving AA2-α-LPHE, AA2-DHC, and AA2-PPR. This research concluded that AA2-DHC was the most stable complex among the investigated interactions, surpassing the stability of the other complexes examined in comparison with the standard drug DOX. Overall, the findings supported the promotion of widespread use of Attukal Kizhangu L. in clinics as a potential therapeutic agent or may be employed for the treatment of acute and chronic Periodontitis. © 2024 Elsevier Ltd
Research and Development of Supramolecules as Anticancer Drugs
(Springer International Publishing, 2023) Manjit; Brahmeshwar Mishra
Cancer has a significant effect on society across the globe, specifically in the United States, which has the highest mortality rate. According to the National Cancer Institute, new cancer es in the United States are expected to exceed 1,918,030 in 2022, with 609,360 fatalities. Despite the fact that several novel drugs have been identified, their in vivo efficacy is restricted due to their extremely lipophilic nature. Furthermore, anticancer drugs have severe toxic or adverse effects on normal cells or tissues. As a result, the quest for a safe and reliable drug entity is essential in order to enhance the drug bioavailability and avoid deleterious effects on normal cells. The supramolecular assembly can be considered such a novel anticancer drug entity to efficiently deliver the drugs with minimal side effects and maximal therapeutic efficacy. Supramolecules can include a variety of nanostructures, layer-by-layer assemblies, conjugates, etc. and offer a high quantitative drug loading and therapeutic release in established carrier degradation and clearance pathways. The modularity of supramolecules also makes it possible to integrate several drugs in a single platform for improved therapeutics outcomes. Supramolecules have tuneable size and shape, which may increase blood circulation, translocation and system efficacy. This chapter will provide a comprehensive insight into the development of various types of supramolecules for cancer therapy, their role in improving the performance of the therapy and regulatory status. Furthermore, the chapter will also shed a light on various targeting strategies that can facilitate the improved translation of supramolecules as anticancer drugs. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2022.