Commenced in January 2007
Frequency: Monthly
Edition: International
Paper Count: 9

doxorubicin Related Publications

9 Monitoring the Effect of Doxorubicin Liposomal in VX2 Tumor Using Magnetic Resonance Imaging

Authors: Ren-Jy Ben, Jo-Chi Jao, Chiu-Ya Liao, Ya-Ru Tsai, Lain-Chyr Hwang, Po-Chou Chen

Abstract:

Cancer is still one of the serious diseases threatening the lives of human beings. How to have an early diagnosis and effective treatment for tumors is a very important issue. The animal carcinoma model can provide a simulation tool for the studies of pathogenesis, biological characteristics, and therapeutic effects. Recently, drug delivery systems have been rapidly developed to effectively improve the therapeutic effects. Liposome plays an increasingly important role in clinical diagnosis and therapy for delivering a pharmaceutic or contrast agent to the targeted sites. Liposome can be absorbed and excreted by the human body, and is well known that no harm to the human body. This study aimed to compare the therapeutic effects between encapsulated (doxorubicin liposomal, Lipodox) and un-encapsulated (doxorubicin, Dox) anti-tumor drugs using magnetic resonance imaging (MRI). Twenty-four New Zealand rabbits implanted with VX2 carcinoma at left thighs were classified into three groups: control group (untreated), Dox-treated group, and LipoDox-treated group, 8 rabbits for each group. MRI scans were performed three days after tumor implantation. A 1.5T GE Signa HDxt whole body MRI scanner with a high resolution knee coil was used in this study. After a 3-plane localizer scan was performed, three-dimensional (3D) fast spin echo (FSE) T2-weighted Images (T2WI) was used for tumor volumetric quantification. Afterwards, two-dimensional (2D) spoiled gradient recalled echo (SPGR) dynamic contrast-enhanced (DCE) MRI was used for tumor perfusion evaluation. DCE-MRI was designed to acquire four baseline images, followed by contrast agent Gd-DOTA injection through the ear vein of rabbit. A series of 32 images were acquired to observe the signals change over time in the tumor and muscle. The MRI scanning was scheduled on a weekly basis for a period of four weeks to observe the tumor progression longitudinally. The Dox and LipoDox treatments were prescribed 3 times in the first week immediately after the first MRI scan; i.e. 3 days after VX2 tumor implantation. ImageJ was used to quantitate tumor volume and time course signal enhancement on DCE images. The changes of tumor size showed that the growth of VX2 tumors was effectively inhibited for both LipoDox-treated and Dox-treated groups. Furthermore, the tumor volume of LipoDox-treated group was significantly lower than that of Dox-treated group, which implies that LipoDox has better therapeutic effect than Dox. The signal intensity of LipoDox-treated group is significantly lower than that of the other two groups, which implies that targeted therapeutic drug remained in the tumor tissue. This study provides a radiation-free and non-invasive MRI method for therapeutic monitoring of targeted liposome on an animal tumor model.

Keywords: Magnetic resonance imaging, doxorubicin, dynamic contrast-enhanced MRI, lipodox, VX2 tumor model

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8 Phage Capsid for Efficient Delivery of Cytotoxic Drugs

Authors: Simona Dostalova, Ana Maria Jimenez Jimenez, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

Abstract:

Various nanomaterials can be used as a drug delivery vehicles in nanomedicine, called nanocarriers. They can either be organic or inorganic, synthetic or natural-based. Although synthetic nanocarriers are easier to produce, they can often be toxic for the organism and thus not suitable for use in treatment. From naturalbased nanocarriers, the most commonly used are protein cages or viral capsids. In this work, virus bacteriophage λ was used for delivery of different cytotoxic drugs (cisplatin, carboplatin, oxaliplatin and doxorubicin). Large quantities of phage λ were obtained from phage λ-producing strain of E. coli cultivated in medium with 0.2% maltose. After killing of E. coli with chloroform and its removal by centrifugation, the phage was concentrated by ultracentrifugation at 130 000×g and 4°C for 3 h. The encapsulation of the drugs was performed by infusion method and four different concentrations of the drugs were encapsulated (200; 100; 50; 25 μg·mL-1). Free drug molecules were removed by filtration. The encapsulation was verified using the absorbance for doxorubicin and atomic absorption spectrometry for platinum cytostatics. The amount of encapsulated drug linearly increased with the increasing concentration of applied drug with the determination coefficient R2=0.989 for doxorubicin; R2=0.967 for cisplatin; R2=0.989 for carboplatin and R2=0.996 for oxaliplatin. The overall encapsulation efficiency was calculated as 50% for doxorubicin; 8% for cisplatin; 6% for carboplatin and 10% for oxaliplatin.

Keywords: doxorubicin, Bacteriophage λ, platinum cytostatics, protein-based nanocarrier, viral capsid

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7 The Toxicity of Doxorubicin with Nanotransporters

Authors: I. Blazkova, A. Moulick, V. Milosavljevic, P. Kopel, M. Vaculovicova, V. Adam, R. Kizek

Abstract:

Doxorubicin (DOX) is an anthracycline drug used to treat many cancer diseases. Similarly to other cytostatic drugs, DOX has serious side effects; the biggest obstacle is the cardiotoxicity. With the aim of lowering the negative side effects and to target the DOX into the tumor tissue, the different nanoparticles (NPs) are studied. The aim of this work was to synthetized different NPs and conjugated them with DOX and determine the binding capacity of the NPs. For this experiment, carbon nanotubes (CNTs), graphene oxide (GO), fullerene (FUL) and liposomes (LIP) were used. The highest binding capacity was observed in GO (85%). Subsequently the toxicity of NPs and NPs-DOX conjugates was analyzed in in vivo system (chicken embryos). Some NPs (GO) can increase the toxicity of DOX, whereas other NPs (LIP, CNTs) decrease DOX toxicity.

Keywords: Toxicity, doxorubicin, chicken embryos, nanotransporters

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6 Gold-Mediated Modification of Apoferritin Surface with Targeting Antibodies

Authors: Simona Dostalova, Pavel Kopel, Marketa Vaculovicova, Vojtech Adam, Rene Kizek

Abstract:

To ensure targeting of apoferritin nanocarrier with encapsulated doxorubicin drug, we used a peptide linker based on a protein G with N-terminus affinity towards Fc region of antibodies. To connect the peptide to the surface of apoferritin, the C-terminus of peptide was made of cysteine with affinity to gold. The surface of apoferritin with encapsulated doxorubicin (APODOX) was coated either with gold nanoparticles (APODOX-Nano) or gold(III) chloride hydrate reduced with sodium borohydride (APODOX-HAu). The reduction with sodium borohydride caused a loss of doxorubicin fluorescent properties and probably accompanied with the loss of its biological activity. Fluorescent properties of APODOX-Nano were similar to the unmodified APODOX; therefore it was more suited for the intended use. To evaluate the specificity of apoferritin modified with antibodies, ELISA-like method was used with the surface of microtitration plate wells coated by the antigen (goat anti-human IgG antibodies). To these wells, the nanocarrier was applied. APODOX without the modification showed 5× lower affinity to the antigen than APODOX-Nano modified gold and targeting antibodies (human IgG antibodies).

Keywords: doxorubicin, nanocarrier, apoferritin, Antibody targeting

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5 Comparative in silico and in vitro Study of N-(1- Methyl-2-Oxo-2-N-Methyl Anilino-Ethyl) Benzene Sulfonamide and Its Analogues as an Anticancer Agent

Authors: Pamita Awasthi, Kirna, Shilpa Dogra, Manu Vatsal, Ritu Barthwal

Abstract:

Doxorubicin, also known as Adriamycin, is an anthracycline class of drug used in cancer chemotherapy. It is used in the treatment of non-Hodgkin’s lymphoma, multiple myeloma, acute leukemia, breast cancer, lung cancer, endometrium cancer and ovary cancers. It functions via intercalating DNA and ultimately killing cancer cells. The major side effects of doxorubicin are hair loss, myelosuppression, nausea & vomiting, oesophagitis, diarrhea, heart damage and liver dysfunction. The minor modifications in the structure of compound exhibit large variation in the biological activity, has prompted us to carry out the synthesis of sulfonamide derivatives. Sulfonamide is an important feature with broad spectrum of biological activity such as antiviral, antifungal, diuretics, antiinflammatory, antibacterial and anticancer activities. Structure of the synthesized compound N-(1-methyl-2-oxo-2-N-methyl anilinoethyl) benzene sulfonamide confirmed by proton nuclear magnetic resonance (1H NMR),13C NMR, Mass and FTIR spectroscopic tools to assure the position of all protons and hence stereochemistry of the molecule. Further we have reported the binding potential of synthesized sulfonamide analogues in comparison to doxorubicin drug using Auto Dock 4.2 software. Computational binding energy (B.E.) and inhibitory constant (Ki) has been evaluated for the synthesized compound in comparison of doxorubicin against Poly (dA-dT).Poly (dA-dT) and Poly (dG-dC).Poly (dG-dC) sequences. The in vitro cytotoxic study against human breast cancer cell lines confirms the better anticancer activity of the synthesized compound over currently in use anticancer drug doxorubicin. The IC50 value of the synthesized compound is 7.12 μM whereas for doxorubicin is 7.2 μM.

Keywords: doxorubicin, anticancer, auto dock, sulfonamide

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4 In vitro and in vivo Anticancer Activity of Nanosize Zinc Oxide Composites of Doxorubicin

Authors: E. R. Arakelova, S. G. Grigoryan, F. G. Arsenyan, N. S. Babayan, R. M. Grigoryan, N. K. Sarkisyan

Abstract:

The nanotechnology offers some exciting possibilities in cancer treatment, including the possibility of destroying tumors with minimal damage to healthy tissue and organs by targeted drug delivery systems. Considerable achievements in investigations aimed at the use of ZnO nanoparticles and nanocontainers in diagnostics and antitumor therapy were described. However, there are substantial obstacles to the purposes to be achieved by the use of zinc oxide nanosize materials in antitumor therapy. Among the serious problems are the techniques of obtaining ZnO nanosize materials. The article presents a new vector delivery system for the known antitumor drug, doxorubicin in the form of polymeric (PEO, starch-NaCMC) hydrogels, in which nanosize ZnO film of a certain thickness are deposited directly on the drug surface on glass substrate by DC-magnetron sputtering of a zinc target. Anticancer activity in vitro and in vivo of those nanosize zinc oxide composites is shown.

Keywords: Anticancer Activity, cancer specificity, doxorubicin, zinc oxide

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3 New Drug Delivery System for Cancer Therapy

Authors: Emma R. Arakelova, Stepan G. Grigoryan, Ashot M. Khachatryan, Karapet E. Avjyan, Lilia M. Savchenko, Flora G. Arsenyan

Abstract:

The paper presents a new drugs delivery system, based on the thin film technology. As a model antitumor drug, highly toxic doxorubicin is chosen. The system is based on the technology of obtaining zinc oxide composite of doxorubicin by deposition of nanosize ZnO films on the surface of doxorubicin coating on glass substrate using DC magnetron sputtering of zinc targets in Ar:O2 medium at room temperature. For doxorubicin zinc oxide compositions in the form of coatings and gels with 180-200nm thick ZnO films, higher (by a factor 2) in vivo (ascitic Ehrlich's carcinoma) antitumor activity is observed at low doses of doxorubicin in comparison with that of the initial preparation at therapeutic doses. The vector character of the doxorubicin zinc oxide composite transport to tumor tissues ensures the increase in antitumor activity as well as decrease of toxicity in comparison with the initial drug.

Keywords: doxorubicin, zinc oxide, antitumor activity, DC magnetron sputtering

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2 Anticancer Effect of Doxorubicin Loaded Heparin based Super-paramagnetic Iron oxide Nanoparticles against the Human Ovarian Cancer Cells

Authors: Amaneh Javid, Shahin Ahmadian, Ali A. Saboury, Saeed Rezaei-Zarchi

Abstract:

This study determines the effect of naked and heparinbased super-paramagnetic iron oxide nanoparticles on the human cancer cell lines of A2780. Doxorubicin was used as the anticancer drug, entrapped in the SPIO-NPs. This study aimed to decorate nanoparticles with heparin, a molecular ligand for 'active' targeting of cancerous cells and the application of modified-nanoparticles in cancer treatment. The nanoparticles containing the anticancer drug DOX were prepared by a solvent evaporation and emulsification cross-linking method. The physicochemical properties of the nanoparticles were characterized by various techniques, and uniform nanoparticles with an average particle size of 110±15 nm with high encapsulation efficiencies (EE) were obtained. Additionally, a sustained release of DOX from the SPIO-NPs was successful. Cytotoxicity tests showed that the SPIO-DOX-HP had higher cell toxicity than the individual HP and confocal microscopy analysis confirmed excellent cellular uptake efficiency. These results indicate that HP based SPIO-NPs have potential uses as anticancer drug carriers and also have an enhanced anticancer effect.

Keywords: Nanoparticles, Ovarian Cancer, doxorubicin, heparin, A2780 cells

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1 Development of a 3D Mathematical Model for a Doxorubicin Controlled Release System using Pluronic Gel for Breast Cancer Treatment

Authors: W. Kaowumpai, D. Koolpiruck, K. Viravaidya

Abstract:

Female breast cancer is the second in frequency after cervical cancer. Surgery is the most common treatment for breast cancer, followed by chemotherapy as a treatment of choice. Although effective, it causes serious side effects. Controlled-release drug delivery is an alternative method to improve the efficacy and safety of the treatment. It can release the dosage of drug between the minimum effect concentration (MEC) and minimum toxic concentration (MTC) within tumor tissue and reduce the damage of normal tissue and the side effect. Because an in vivo experiment of this system can be time-consuming and labor-intensive, a mathematical model is desired to study the effects of important parameters before the experiments are performed. Here, we describe a 3D mathematical model to predict the release of doxorubicin from pluronic gel to treat human breast cancer. This model can, ultimately, be used to effectively design the in vivo experiments.

Keywords: Breast Cancer, doxorubicin, Controlled ReleaseSystem, Diffusion and Convection Equation

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