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Isfahan University of Medical Sciences
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| Document Type
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Latin Dissertation
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| Language of Document
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English
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| Record Number
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103179
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| Doc. No
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T14507
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| Call number
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QV,269,F527p,2014
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| Main Entry
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Firozian, Farzin
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| Title & Author
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Preparation and characterization of folate targeted dextran-stearate micelles for delivery of Etoposide in colorectal cancer/فرزین فیروزان
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| College
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Schools, Pharmacy
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| Date
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, 2014
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| Degree
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Pharmaceutics, Ph.D
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| Page No
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k, 122 p.: ill., diag. tab
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| Note
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This is a dissertation research with project ID: 389390
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| Abstract
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One of the strategies for reduction of chemotherapy drugs side effects is targeted drug delivery systems. The folate receptor is a valuable highly expressed therapeutic target on a variety of cancers. The main aim of this work was evaluation of folate grafted copolymer dextran stearate (FDS) as a potential etoposide carrier. Dextran stearate (DS) and FDS were synthesized. FT-IR and NMR spectroscopy were used to confirm successful conjugation. Micelles that prepared using this copolymer were characterized for their particle size, zeta potential, critical micelle concentration (CMC), drug loading capacity and release efficiency. Cytotoxicity and cellular uptake of the micelles were estimated using CT-26 cell line. In order to establishing colorectal cancer animal model , 2* 10 (6 ) cells in PBS were injected subcutaneously into the left flank of Balb C mice. Saline, free etoposide (10 mg/kg), blank and etoposide loaded micelles were injected intravenously into the mice each 2 days in four doses. The mortality and tumor growth of the mice were monitored each two day. Pharmacokinetics and tissue distribution of etoposide and etoposide loaded FDS polymeric micelles following i.v. (bolus) injection (10 mg/kg) were assessed in tumor bearing mice by HPLC. IC50 of etoposide loaded in FDS enhanced about 20 fold compared to the pure drug (0.49 + - 0.11 mg/mL vs. 9.41+- 0.52 mg/mL). Tumor size in group that had received drug loaded FDS nanoparticles significantly smaller than mice which have received etoposide loaded DS (P< 0.05). Area under the curve of lung tissue concentrations vs. time was significantly higher in etoposide loaded FDS received animals. While that parameter for kidney and heart tissues were significantly higher in etoposide injected mice. Molecular weight and molar ratio of dextran/stearic acid were impressive on zeta potential, CMC, drug loading capacity, and release efficiency of the DS. It seems etoposide loaded in micelles FDS copolymer are promising in reducing drug resistance of colorectal cancer by boosting etoposide cellular uptake. Formulation of etoposide in the FDS polymeric micelles has changed the drug pharmacokinetic profile in initial distribution phase mostly, and has no significant effect in the terminal excretion phase of the drug pharmacokinetic profile.
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| Descriptor
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1. Antineoplastic Agents.- Descriptors: Antineoplastic Agents
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Dextrans
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Folic Acid
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Etoposide
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Colorectal Neoplasms
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Drug Delivery Systems
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| Added Entry
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Varshosaz, Jaleh, Supervisor
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Hassanzadeh, Farshid, Supervisor
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Sadeghi Aliabadi, Hojjat, Supervisor
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Minaiyan, Mohsen, Supervisor
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| Translated Title Supplied by Cataloguer
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تهیه و ارزیابی میسل هیا هدفمند شده با فولات از دکستران استئارات جهت دارورسانی اتوپوساید به سرطان کولورکتال
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http://elib.mui.ac.ir/site/catalogue/103179
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