DSpace at EWHA: Synthesis and Characterization of Water Soluble Phosphazene Trimer-Taxol Ion Pair Adducts and Conjugates

Browse

My Repository

DSpace at EWHA일반대학원 화학·나노과학과 Theses_Master

View : 624 Download: 0

Full metadata record

DC Field	Value	Language
dc.contributor.advisor	손연수	-
dc.contributor.author	유진희	-
dc.creator	유진희	-
dc.date.accessioned	2016-08-25T01:08:38Z	-
dc.date.available	2016-08-25T01:08:38Z	-
dc.date.issued	2005	-
dc.identifier.other	OAK-000000010288	-
dc.identifier.uri	https://dspace.ewha.ac.kr/handle/2015.oak/172051	-
dc.identifier.uri	http://dcollection.ewha.ac.kr/jsp/common/DcLoOrgPer.jsp?sItemId=000000010288	-
dc.description.abstract	Paclitaxel (Taxol) is a diterpenoid isolated from Taxus brevifolia, used clinically for treatment of ovarian and breast cancer. Due to its aqueous insolubility it is administered dissolved in ethanol and Cremophore EL(polyethoxylated caster oil), which has serious side effects. Water soluble cyclotriphosphazene derivatives have been studied in order to improve water solubility and the chemotherapeutical potency of paclitaxel. Cyclotriphosphazene derivatives were synthesized by stepwise nucleophilic substitutions of hexachlorocyclotriphosphazene with a hydrophilic poly(ethylene glycol) as a solubilizing group and lysine as a spacer group. They were found to form a micelle in the presence of 2′-succinyl taxol. It is presumed that the cyclic trimer may form an ion pair adduct with carboxylic acid of 2′-succinyl taxol through the alpha-amine group of lysine. We also synthesized water soluble cyclotriphosphazene taxol conjugates. The in vitro cytotoxic activities of IPA and conjugate are very low.	-
dc.description.tableofcontents	Table of Contents Table of Contents = ⅰ List of Figures = ⅳ List of Schemes = ⅵ List of Tables = ⅶ List of Abbreviations = ⅷ Chapter 1. Introduction = 1 1.1. Polymeric drug delivery systems = 2 1.2. Biodegradable Polymers = 4 1.3. Polyphosphazenes = 6 1.3.1. Introduction = 6 1.3.2. Cyclotriphosphazene의 특성 = 7 1.3.3. Poly(organophosphazene)의 특성 = 10 1.4. Taxol as an anticancer agent = 13 1.4.1. History of the development of taxol = 13 1.4.2. The mechanism of taxol's activity = 15 1.4.3. Toxicity and side-effects = 17 1.4.4. Structure activity relationship (SAR) of taxol analogs = 18 1.5. Goals of this study = 19 1.6. References = 21 Chapter 2. Drug assisted micelle formation of hydrophilic cyclotriphosphazene = 25 2.1. Introduction = 26 2.2. Experimental section = 31 2.2.1. Materials = 31 2.2.2. Instruments = 31 2.2.3. Synthesis and characterization = 32 (가) Lysine ethylester = 32 (나) [NP(MPEG350)LysEt]₃(1) = 32 (다) [NP(MPEG550)LysEt]₃(2) = 33 (라) 2′-Succinyltaxol (3) = 34 2.2.4. Methods of ion pair aduct preparation = 35 2.2.5. Micelle size and size distribution = 36 2.2.6. Zeta potential = 36 2.2.7. Determination of critical micelle concentration = 37 2.2.8. Cytotoxicity data = 37 2.3. Results and discussion = 39 2.3.1. Synthesis and characterization = 39 2.3.2. Mechanism of micelle formation = 46 2.3.3. Micelle size and size distribution = 52 2.3.4. Critical micelle concentration(CMC) = 53 2.3.5. Cytotoxicity data = 55 2.4. Conclusions = 57 2.5 References = 58 Chapter 3. Design and Synthesis of Water Soluble Cyclotriphosphazene-Paclitaxel conjugates = 60 3.1. Introduction = 61 3.2. Experimental Section = 64 3.2.1. Materials = 64 3.2.2. Instruments = 65 3.2.3. Synthesis and characterization = 65 (가) [NP(MPEG350)LysEt·2'-succinyltaxol]₃(4) = 65 (나) [{NP(MPEG350)LysEt·2'′-succinyltaxol}₁{NP(MPEG350)LysEt}₂]₃(5) = 66 (다) [NP(MPEG550)LysEt·2'-succinyltaxol]₃(6) = 67 (라)[{NP(MPEG550)LysEt·2'-succinyltaxol}₁{NP(MPEG550)LysEt}₂]₃(7) = 68 3.2.4. Micelle size and size distribution = 69 3.2.5. Determination of critical micelle concentration = 70 3.2.6. Cytotoxicity data = 70 3.3 Results and discussion = 71 3.3.1. Synthesis and characterization = 71 3.3.2. Micelle size and size distribution = 77 3.3.3. Critical micelle concentration(CMC) = 78 3.3.4. Cytotoxicity data = 80 3.4. Conclusions = 82 3.5. References = 83 Abstract = 85	-
dc.format	application/pdf	-
dc.format.extent	1548912 bytes	-
dc.language	kor	-
dc.publisher	이화여자대학교 대학원	-
dc.subject	phosphazene	-
dc.subject	phosphazene trimer	-
dc.subject	biodegradable	-
dc.subject	paclitaxel	-
dc.subject	oligomeric micelle	-
dc.subject	ion pair adduct	-
dc.subject	drug conjugate	-
dc.subject	critical micelle concentration	-
dc.subject	cytotoxicity	-
dc.title	Synthesis and Characterization of Water Soluble Phosphazene Trimer-Taxol Ion Pair Adducts and Conjugates	-
dc.type	Master's Thesis	-
dc.creator.othername	Yoo, Jin Hee	-
dc.format.page	x, 86 p.	-
dc.identifier.thesisdegree	Master	-
dc.identifier.major	대학원 나노과학부	-
dc.date.awarded	2005. 8	-