School Of Basic And Applied Sciences
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Item Biodegradable nanoparticulate co-delivery of flavonoid and doxorubicin: Mechanistic exploration and evaluation of anticancer effect in vitro and in vivo(Elsevier Ltd, 2021-07-30T00:00:00) Khan, Iliyas; Sarkar, Bibekananda; Joshi, Gaurav; Nakhate, Kartik T.; Ajazuddin; Mantha, Anil K.; Kumar, Raj; Kaul, Ankur; Chaturvedi, Shubhra; Mishra, Anil K.; Gupta, UmeshThe proposed study involves delivering drug/bioactive using a single nanoplatform based on poly lactic-co-glycolic acid (PLGA) for better efficacy, synergistic effect, and reduced toxicity. PLGA was conjugated to doxorubicin (D1), and this conjugate was used for encapsulation of naringenin (D2) to develop naringenin loaded PLGA-doxorubicin nanoparticles (PDNG). The PDNG NPs were 165.4 � 4.27 nm in size, having 0.112 � 0.035 PDI, with -10.1 � 2.74 zeta potential. The surface morphology was confirmed through transmission electron microscopy (TEM) and atomic force microscopy (AFM). The in vitro studies revealed that PDNG NPs exhibited selective anticancer potential in breast cancer cells, and induced apoptosis with S-phase inhibition via an increase in intrinsic reactive oxygen species (ROS) and altering the mitochondrial potential. The results also signified the efficient uptake of nanoparticles encapsulated drugs by cells besides elevating the caspase level suggesting programmed cell death induction upon treatment. In vivo studies results revealed better half-life (27.35 � 1.58 and 11.98 � 1.21 h for doxorubicin and naringenin) with higher plasma drug concentration. In vivo biodistribution study was also in accordance with the in vitro studies and in line with the in vivo pharmacokinetic. In vivo tumor regression assay portrayed that the formulation PDNG halts the tumor growth and lessen the tumor volume with the stable bodyweight of the mice. Conclusively, the dual delivery approach was beneficial and highly effective against tumor-induced mice. � 2021 The Author(s)Item Exploring insights of hydroxychloroquine, a controversial drug in Covid-19: An update(Elsevier Ltd, 2021-03-18T00:00:00) Joshi, Gaurav; Thakur, Shikha; Mayank; Poduri, RamaraoThe review summarizes chloroquine (CQ) and its safer derivative hydroxychloroquine (HCQ) and its utility in Covid-19. Recently this well-established drug made its way back to the headlines during the SARS-CoV-2 pandemic. This led to an upsurge in the scientific arena with multiple research and review articles along with expert opinions and commentaries. The HCQ has received mixed judgements so far about its efficacy to be used in Covid-19 patients in a limited trial conducted all across the Globe. The purpose of our article is to put forth the history, pharmacodynamics, and pharmacokinetics, along with the existing studies favouring and disapproving the role of HCQ in the treatment of Covid-19. We grouped HCQ use at three stages, this includes HCQ for i. prophylactic use by asymptomatic health workers or peoples at higher risk; ii. patients having mild symptoms; iii. patients with extreme symptoms. The review critically discusses the underlying plausible reasons and mechanisms exploring HCQ in prophylactic management or treatment of SARS-CoV-2. Furthermore, we have critically analysed the reported pharmacokinetic parameters and compiled the proponent, opponent, or neutral opinions on the use of HCQ in Covid-19. Authors discretion is to conduct more studies considering the optimal dosing regimen and pharmacokinetics assessment. � 2021 Elsevier LtdItem Drug Discovery and Development: From Targets and Molecules to Medicines(Springer Singapore, 2021-02-18T00:00:00) Poduri, RamaraoThis book describes the processes that are involved in the development of new drugs. The authors discuss the history, role of natural products and concept of receptor interactions with regard to the initial stages of drug discovery. In a single, highly readable volume, it outlines the basics of pharmacological screening, drug target identification, and genetics involved in early drug discovery. The final chapters introduce readers to stem therapeutics, pharmacokinetics, pharmacovigilance, and toxicological testing. Given its scope, the book will enable research scholars, professionals and young scientists to understand the key fundamentals of drug discovery, including stereochemistry, pharmacokinetics, clinical trials, statistics and toxicology. � Springer Nature Singapore Pte Ltd. 2021.Item Transport and metabolism of tyrosine kinase inhibitors associated with chronic myeloid leukemia therapy: a review(Springer, 2022-02-07T00:00:00) Kumar, Veerandra; Singh, Priyanka; Gupta, Sonu Kumar; Ali, Villayat; Verma, MalkheyImatinib, nilotinib, dasatinib, bosutinib, ponatinib, and asciminib are FDA-approved tyrosine kinase inhibitors (TKIs) for chronic myeloid leukemia (CML), each of which has a specific pharmacological profile. Asciminib has been recently (2021) approved for patients resistant to former TKIs, and because the binding site of this drug (the myristoyl pocket in the ABL1 kinase) is different from that of other TKIs (ATP-binding sites), it is, therefore, effective against T315I mutation of BCR-ABL oncoprotein. All TKIs have a different pharmacological profile due to different chemical structures. Imatinib is the only TKI whose absorption depends on both influx (OCT1 and OATP1A2) and efflux (ABCB1 and ABCG2) transporters, whereas the others rely only on efflux transporters. The efflux of dasatinib is also regulated by ABCC4 and ABCC6 transporters. Nilotinib and ponatinib are transported passively, as no role of transporters has been found in their case. A phenomenon common to all in the metabolic aspect is that the CYP3A4 isoform of CYP450 primarily metabolizes TKIs. Not only does CYP3A4, flavin-containing monooxygenase 3 (FMO3), and uridine 5'-diphospho-glucuronosyltransferase (UGT) also metabolize dasatinib, and similarly, by glucuronidation process, asciminib gets metabolized by UGT enzymes (UGT1A3, UGT1A4, UGT2B7, and UGT2B17). Additionally, the side effects of TKIs are categorized as hematological (thrombocytopenia, neutropenia, anemia, and cardiac dysfunction) and non-hematological (diarrhea, nausea, vomiting, pleural effusion, and skin rash). However, few toxicities are drug-specific, like degradation of biomolecules by ponatinib-glutathione (P-GSH) conjugates and clinical pancreatitis (dose-limited toxicity and manageable by dosage alterations) are related to ponatinib and asciminib, respectively. This review focuses on the pharmacokinetics of approved TKIs related to CML therapy to comprehend their specificity, tolerability, and off-target effects, which could help clinicians to make a patient-specific selection of CML drugs by considering concomitant diseases and risk factors to the patients. � 2022, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.