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dc.contributor.advisor손연수-
dc.contributor.author성지연-
dc.creator성지연-
dc.date.accessioned2016-08-25T04:08:41Z-
dc.date.available2016-08-25T04:08:41Z-
dc.date.issued2004-
dc.identifier.otherOAK-000000009702-
dc.identifier.urihttps://dspace.ewha.ac.kr/handle/2015.oak/176649-
dc.identifier.urihttp://dcollection.ewha.ac.kr/jsp/common/DcLoOrgPer.jsp?sItemId=000000009702-
dc.description.abstractA new class of thermosensitive poly(organophosphazene) gels were synthesized by stepwise nucleophilic substitutions of poly(dichlorophosphazene) with methoxy-poly(ethylene glycol) (MPEG) and highly hydrophobic tri- or tetrapeptides such as GlyPheIleEt, GlyPheLeuEt, GlyLeuPheEt, and GlyPheLeuGlyEt as side groups and characterized by means of multinuclear (^(1)H, ^(31)P) NMR spectroscopy, gel permeation chromatography, and elemental analysis. Their temperature-dependent sol-gel properties were investigated by viscometer. In an aqueous solution, the poly(organophosphazenes) exhibited four-phase transitions with increasing temperature: a transparent sol, a transparent gel, an opaque gel, and a turbid sol. The gelation properties of the polymer were affected by several factors such as the composition of substituents, the hydrophobicity of the oligopeptides, and the concentration of the polymer solutions. The more hydrophilic composition of the polymers resulted in the higher gelation temperature. The gelation of the polymer is presumed to be attributed to the hydrophobic interaction between the hydrophobic oligopeptide side groups, which form the physical junction zone in the polymer aqueous solution. Water soluble poly(organophosphazenes) with LCST were synthesized by introducing hydrophilic methoxy poly(ethylene glycols) and various hydrophobic oligopeptide ethyl esters as side groups into the phosphazene backbone. These polymers exhibit lower critical solution temperatures (LCST) in the range of 25-81 °C and biodegradability, which can afford applications to a variety of drug delivery systems. The hydrolytic properties of the poly(organophosphazenes) have been studied at different pHs by means of gel permeation chromatography. The polymer hydrolysis occurred more rapidly in acidic buffer solution than in the neutral and basic solutions. The biocompatibility, release profiles of poly(organophosphazenes) loaded with hGH were studied. The biocompatible and thermosensitive poly(organophosphazenes) with a LCST around body temperature showed potential as an excellent carrier candidate for hydrophobic drugs such hGH.;친수성기인 폴리에틸렌글라이콜과 소수성인 올리고펩타이드 에스터를 곁사슬로 갖는 온도감응성 폴리포스파젠을 합성하였고 이 고분자의 솔-젤 특성을 점도계와 핵자기 공명법을 이용해서 조사하였다. 이들 고분자는 수용액상에서 온도변화에 따라 네 가지의 상태 변화를 보이는데 온도가 증가함에 따라 투명한 솔, 투명한 젤, 불투명한 젤, 그리고 탁한 솔의 상태로 변화하였다. 이들 고분자의 젤 특성은 고분자 수용액의 농도와 올리고펩타이드의 종류에 따라 변화하였다. 친수성 특성이 강한 고분자일수록 젤이 되는 온도가 증가하였다. 폴리포스파젠의 젤 형성 메커니즘은 고분자 수용액에서 곁사슬인 올리고펩타이드의 소수성 부분이 온도 변화에 따른 소수성 상호작용으로 물리적 가교를 형성하는 것으로 추정된다. 폴리포스파젠 젤은 단백질 및 펩타이드 등과 같은 유기용매와 온도 변화에 의해 쉽게 변성되는 약물의 국부 전달체로서의 응용이 기대된다. 친수성기로 메톡시폴리에틸렌글라이콜과 소수성기로 소수성이 높은 올리고펩타이드를 곁가지로 갖는 폴리포스파젠을 합성하였다. 이들 고분자는 25-81 °C 사이의 LCST를 갖고 생체분해성이어서 다양한 약물의 전달체로의 응용이 기대된다. 폴리포스파젠 수용액의 분해를 다양한 pH에서 GPC를 통해 측정하였다 산성 완충용액에서의 분해 속도가 중성, 염기성 완충용액에 비해 빨랐다. hGH가 함유된 폴리포스파젠의 생체적합성과 약물 방출 속도를 측정하였다. 이 고분자들은 성장 호르몬과 같은 소수성 약물의 전달체로 응용될 수 있는 가능성이 매우 높다.-
dc.description.tableofcontentsTable of Contents List of Figures = ⅴ List of Schemes = ⅷ List of Tables = ⅸ List of Abbreviations = ⅹ Abstract = xi CHAPTER 1. Introduction = 1 1.1. Polymeric Drug Delivery Systems = 2 1.2. Biodegradable Polymers = 4 1.3. Thermosensitive Hydrogels = 6 1.4. Polyphosphazenes = 8 1.4.1. Introduction = 8 1.4.2. Synthesis = 9 1.4.3. Physical Properties = 12 1.4.3.1. Ring Opening Polymerization of Cyclotriphosphazene = 12 1.4.3.2. Backbone Flexibility = 15 1.5. Thermosensitive Polymers = 17 1.5.1. Thermosensitivity = 17 1.5.2. Uses of Thermosensitive Polymers = 21 1.5.3. Measurement of Thermosensitivity = 21 1.6. Characteristic Features of Amino Acids = 23 1.7. Goals of this Study = 26 1.8. References = 27 CHAPTER 2. A New Class of Thermosensitive Poly(organophosphazene) Gels. Synthesis and Characterization of Poly(organophosphazenes) with Methoxy-Poly(ethylene glycol) and Oligopeptides as Side Groups = 29 2.1. Abstract = 30 2.2. Introduction = 31 2.3. Experimental Section = 33 2.3.1. Materials = 33 2.3.2. Synthesis = 34 2.3.2.1. [NP(MPEG350)_(1.00)(GlyPheIleEt)_(1.00)]_(n)·2H₂O(1). = 34 2.3.2.2. [NP(MPEG350)_(0.80)(GlyPheIleEt)_(1.20)]_(n)·2H₂O(2). = 35 2.3.2.3. [NP(MPEG350)_(1.10)(GlyPheIleEt)_(0.90)]_(n)·2H₂O(3). = 35 2.3.2.4. [NP(MPEG350)_(1.02)(GlyPheLeuEt)_(0.98)]_(n)·2H₂O(4). = 36 2.3.2.5. [NP(MPEG350)_(0.80)(GlyLeuPheEt)_(1.20)]_(n)·2H₂O(5). = 36 2.3.2.6. [NP(MPEG350)_(0.70)(GlyLeuPheEt)_(1.30)]_(n)·3H₂O(6). = 36 2.3.2.7. [NP(MPEG350)_(1.00)(GlyPheLeuGlyEt)_(1.00)]_(n)·2H₂O(7). = 37 2.3.3. Instruments and Measurements = 37 2.4. Results and Discussion = 39 2.4.1. Synthesis and Characterization. = 39 2.4.2. Thermosensitive Properties. = 44 2.5. Conclusions = 48 2.6. References = 48 Chapter 3. Synthesis, Characterization, Biocompatibility and Drug Releasing Profiles of Biodegradable Thermosensitive Poly(organophosphazenes) with Methoxy-Poly(ethylene glycol) and Oligopeptide Ethyl Esters as Side Groups = 51 3.1. Introduction = 52 3.2. Experimental Section = 56 3.2.1. Materials = 56 3.2.2. Instruments = 56 3.2.3. Animals = 57 3.2.4. Synthesis = 57 3.2.4.1. [NP(MTriEG)_(0.85)(GlyGlu(Et₂)_(1.15))]_(n)(1). = 58 3.2.4.2. [NP(MTetEG)_(0.95)(GlyGlu(Et₂)_(1.05))]_(n)(2). = 59 3.2.4.3. [NP(MPEG350)_(1.05)(GlyGluEt₂)_(0.95)]_(n)(3). = 59 3.2.4.4. [NP(MPEG350)_(0.78)(GlyPhe(Et)_(1.22))]_(n)(4). = 59 3.2.4.5. [NP(MPEG350)_(1.10)(GlyPheAsp(Et₂)_(0.90))]_(n)(5). = 60 3.2.5. Hydrolytic Degradation of Poly(organophosphazenes) = 60 3.2.6. The Stability and Entrapment Efficiency of hGH in Polymer Solutions = 60 3.2.7. Biocompatibility Test = 61 3.2.8. In Vitro Drug Release = 61 3.2.9. In Vivo Drug Release = 62 3.3. Results and Discussion = 63 3.3.1. Synthesis and Characterization = 63 3.3.2. Thermosensitivity = 66 3.3.3. Hydrolytic Behavior = 71 3.3.4. The Stability and Entrapment efficiency of hGH in Polymer Solutions = 73 3.3.5. Biocompatibility Test = 73 3.3.6. In Vitro Drug Release = 77 3.3.7. In Vivo Drug Release = 78 3.4. Conclusions = 79 3.5. References = 81 국문요약 = 84 감사의 글 = 86-
dc.formatapplication/pdf-
dc.format.extent894524 bytes-
dc.languageeng-
dc.publisher이화여자대학교 대학원-
dc.subjectPolyphosphazene-
dc.subjectsol-gel-
dc.subjectLCST-
dc.subjectdrug delivery systems-
dc.subjectHgh-
dc.titleSynthesis, Characterization, and Properties of Thermosensitive Polyphosphazene Sol-Gel Systems-
dc.typeMaster's Thesis-
dc.title.translated온도감응성 폴리포스파젠 졸-겔 시스템의 합성과 물성-
dc.creator.othernameSeong, Ji Yeon-
dc.format.pageⅹ, 87 p.-
dc.identifier.thesisdegreeMaster-
dc.identifier.major대학원 나노과학부-
dc.date.awarded2005. 2-
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