School Of Basic And Applied Sciences

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Subject: search.filters.subject.Doxorubicin

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    Thiolated ?-cyclodextrin modified iron oxide nanoparticles for effective targeted cancer therapy
    (Elsevier Ltd, 2022-10-13T00:00:00) Nayak, Jyotsnamayee; Prajapati, Kumari Sunita; Kumar, Shashank; Vashistha, Vinod Kumar; Sahoo, Suban K.; Kumar, Rajender
    Inspired by the mitochondria iron-sulfur protein, direct functionalization of thiolated ?-cyclodextrin (?-CD-SH) on iron oxide nanoparticles (IONPs) through Fe-S bond was done. The resulting system had an average size of 14 nm with an ellipsoidal shape. The X-Ray photoelectron spectroscopy (XPS) confirmed the formation of the Fe-S bond. Doxorubicin (DOX) was chosen as a model drug, about 12.45 �M/mg entrapped in ?-CD-SH coated IONPs (T?CD-IONPs). The hybrid nanocarrier possessed high stability and drug loading efficiency. The invitro release data revealed an overall sustainable release profile without initial bust. The Higuchi kinetic model best fits the release mechanism, based on diffusion action in dosages proportional to the square root of time. The surface coating and particle size have a crucial role in the cellular responses and effective toxic mechanisms. The cellular internalization of drug-loaded nanoparticles (NPs) into the breast cancer cell line MCF-07 was done using MTT assay and confocal imaging. The prepared system shows high performance with an IC50 value at 67 nM of nanoparticle concentration. The prepared nanoparticles are promising candidates for the effective targeted delivery of hydrophobic drugs with enhanced theragnostic activity. � 2022 Elsevier Ltd
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    Glycyrrhiza glabra (Licorice) root extract attenuates doxorubicin-induced cardiotoxicity via alleviating oxidative stress and stabilising the cardiac health in H9c2 cardiomyocytes
    (Elsevier, 2020) Upadhyay, S; Mantha, A.K; Dhiman, Monisha
    Ethnopharmacological relevance: Doxorubicin (DOX) is an effective anti-neoplastic drug, however; it has downside effects on cardiac health and other vital organs. The herbal remedies used in day to day life may have a beneficial effect without disturbing the health of the vital organs. Glycyrrhiza glabra L. is a ligneous perennial shrub belonging to Leguminosae/Fabaceae/Papilionaceae family growing in Mediterranean region and Asia and widespread in Turkey, Italy, Spain, Russia, Syria, Iran, China, India and Israel. Commonly known as mulaithi in north India, G. glabra has glycyrrhizin, glycyrrhetic acid, isoliquiritin, isoflavones, etc., which have been reported for several pharmacological activities such as anti-demulcent, anti-ulcer, anti-cancer, anti-inflammatory and anti-diabetic. Aim of the study: The objective of the present study is to investigate the interaction between the molecular factors like PPAR-?/? and SIRT-1 during cardiac failure arbitrated by DOX under in vitro conditions and role of Glycyrrhiza glabra (Gg) root extract in alleviating these affects. Materials and methods: In the present study, we have examined the DOX induced responses in H9c2 cardiomyocytes and investigated the role of phytochemical Glycyrrhiza glabra in modulating these affects. MTT assay was done to evaluate the cell viability, Reactive Oxygen Species (ROS)/Reactive Nitrogen Species (RNS) levels, mitochondrial ROS, mitochondrial membrane potential was estimated using fluorescent probes. The oxidative stress in terms of protein carbonylation, lipid peroxidation and DNA damage was detected via spectrophotometric methods and immune-fluorescence imaging. The cardiac markers and interaction between SIRT-1 and PPAR-?/? was measured using Real-Time PCR, Western blotting and Co-immunoprecipitation based studies. Results: The Glycyrrhiza glabra (Gg) extracts maintained the membrane integrity and improved the lipid homeostasis and stabilized cytoskeletal element actin. Gg phytoextracts attenuated aggravated ROS level, repaired the antioxidant status and consequently, assisted in repairing the DNA damage and mitochondrial function. Further, the expression of hypertrophic markers in the DOX treated cardiomyocytes reconciled the expression factors both at the transcriptional and translational levels after Gg treatment. SIRT-1 mediated pathway and its downstream activator PPARs are significant in maintaining the cellular functions. It was observed that the Gg extract allows regaining the nuclear SIRT-1 and PPAR-? level which was otherwise reduced with DOX treatment in H9c2 cardiomyocytes. The co-immunoprecipitation (Co-IP) documented that SIRT-1 interacts with PPAR-? in the untreated control H9c2 cardiomyocytes whereas DOX treatment interferes and diminishes this interaction however the Gg treatment maintains this interaction. Knocking down SIRT-1 also downregulated expression of PPAR-? and PPAR-? in DOX treated cells and Gg treatment was able to enhance the expression of PPAR-? and PPAR-? in SIRT-1 knocked down cardiomyocytes. Conclusions: The antioxidant property of Gg defend the cardiac cells against the DOX induced toxicity via; 1) reducing the oxidative stress, 2) maintaining the mitochondrial functions, 3) regulating lipid homeostasis and cardiac metabolism through SIRT-1 pathway, and 4) conserving the cardiac hypertrophy and hence preserving the cardiomyocytes health. Therefore, Gg can be recommended as a healthy supplement with DOX towards cancer therapeutics associated cardiotoxicity. - 2020
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    Augmented anticancer efficacy of doxorubicin-loaded polymeric nanoparticles after oral administration in a breast cancer induced animal model
    (2011) Jain, A.K.; Swarnakar, N.K.; Das, M.; Godugu, C.; Singh, R.P.; Rao, P.R.; Jain, S.
    The present investigation reports an extensive evaluation of in vitro and in vivo anticancer efficacy of orally administered doxorubicin-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles (Dox-NPs) in a breast cancer induced animal model. Spherically shaped Dox-NPs were prepared with an entrapment efficiency and particle size of 55.40 ? 2.30% and 160.20 ? 0.99 nm, respectively, and freeze-dried with 5% trehalose using stepwise freeze-drying. Cytotoxicity, as investigated on C127I cell line, revealed insignificant differences between the IC 50 of free Dox and Dox-NPs treated cells in the first 24 h, while higher cytotoxicity was demonstrated by Dox-NPs, following 72 h of incubation. Confocal laser scanning microscopy (CLSM) imaging corroborated that nanoparticles were efficiently localized into the nuclear region of C127I cells. The cellular uptake profile of Dox-NPs revealed both time and concentration dependent increases in the Caco-2 cell uptake as compared to the free Dox solution. Further, Dox-NPs significantly suppressed the growth of breast tumor in female Sprague-Dawley (SD) rats upon oral administration. Finally, orally administered Dox-NPs showed a marked reduction in cardiotoxicity when compared with intravenously injected free Dox as also evident by the increased level of malondialdehyde (MDA), lactate dehydrogenase (LDH), and creatine phosphokinase (CK-MB) and reduced levels of glutathione (GSH) and superoxide dismutase (SOD). The reduced cardiotoxicity of orally administered Dox-NPs was also confirmed by the major histopathological changes in the heart tissue after the treatments of intravenously injected free Dox and orally delivered Dox-NPs. ? 2011 American Chemical Society.
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    Intracellular delivery of redox cycler-doxorubicin to the mitochondria of cancer cell by folate receptor targeted mitocancerotropic liposomes
    (2012) Malhi, Sarandeep Singh; Budhiraja, Abhishek; Arora, Sumit; Chaudhari, Kiran R.; Nepali, Kunal; Kumar, Raj; Sohi, Harmik; Murthy, Rayasa S.R.
    Cancer cells reflect higher level of ROS in comparison to the normal cell, so they become more vulnerable to further oxidative stress induced by exogenous ROS-generating agents. Through this a novel therapeutic strategy has evolved, which involves the delivery of redox cycler-doxorubicin (DOX) to the mitochondria of cancer cell where it acts as a source of exogenous ROS production. The purpose of this study is to develop a liposomal preparation which exhibits a propensity to selectively target cancer cell along with the potential of delivering drug to mitochondria of cell. We have rendered liposomes mitocancerotropic (FA-MTLs) by their surface modification with dual ligands, folic acid (FA) for cancer cell targeting and triphenylphosphonium (TPP) cations for mitochondria targeting. The cytotoxicity, ROS production and cell uptake of doxorubicin loaded liposomes were evaluated in FR (+) KB cells and found to be increased considerably with FA-MTLs in comparison to folic acid appended, mitochondria targeted and non-targeted liposomes. As confirmed by confocal microscopy, the STPP appended liposomes delivered DOX to mitochondria of cancer cell and also showed higher ROS production and cytotoxicity in comparison to folic acid appended and non-targeted liposomes. Most importantly, mitocancerotropic liposomes showed superior activity over mitochondria targeted liposomes which confirm the synergistic effect imparted by the presence of dual ligands - folic acid and TPP on the enhancement of cellular and mitochondrial delivery of doxorubicin in KB cells. ? 2012 Elsevier B.V. All rights reserved.