成功大學博碩士論文系統

簡易檢索 / 詳目顯示

回結果列表

研究生：	黃筠喬 Huang, Yun-Chiao
論文名稱：	醣聚胺酸高分子之合成、自組裝與應用 Synthesis, self-assembly, and application of glycopolypeptides
指導教授：	詹正雄 Jan, Jeng-Shiung
學位類別：	博士 Doctor
系所名稱：	工學院 - 化學工程學系 Department of Chemical Engineering
論文出版年：	2014
畢業學年度：	102
語文別：	英文
論文頁數：	118
中文關鍵詞：	醣聚胺酸高分子、幾丁聚醣衍生物、自組裝、奈米粒子、聚苯基穀胺酸
外文關鍵詞：	glycopolypeptides, chitosan derivatives, self-assembly, nanoparticles, PBLG
相關次數：	點閱：83 下載：1
分享至:	分享至facebook 分享至twitter

查詢本校圖書館目錄查詢臺灣博碩士論文知識加值系統勘誤回報

近年來，功能性高分子奈米粒子受到極大的重視，主要是因功能性高分子奈米粒子具有多樣化的組裝型態，且已廣泛地被應用於生醫領域。本研究目的是發展醣類-聚胺基酸高分子系統，並評估其應用於生醫領域之可行性。本研究第一部分是合成聚賴胺酸接枝六碳鏈高分子及評估其包覆攜氧蛋白質之可行性。聚賴胺酸接枝六碳鏈高分子於水相中的自組裝行為受到六碳鏈接枝率及高分子鏈二級結構變化的影響。實驗結果顯示聚賴胺酸接枝六碳鏈高分子於水相中形成高分子液胞組裝結構，且高分子液胞粒徑大小(100~500 nm)及二級結構變化受到環境酸鹼值影響。高分子液胞含有一水相隔間，能包覆肌紅素，未來極具潛力應用於蛋白質包覆體。此高分子液胞以梔子素進行部分交聯，可得到較穩定之高分子液胞結構。
本研究第二部分是將半乳糖修飾於聚賴胺酸接枝六碳鏈高分子，並評估其應用於抗癌藥物傳遞系統之可行性。實驗結果顯示半乳糖及六碳鏈接枝率影響高分子液胞粒徑大小及高分子鏈二級結構變化。由第一部份研究可知高分子液胞經由梔子素交聯後，高分子液胞結構較穩定。進一步地，藉由高分子液胞內外酸鹼值梯度效應，能有效地將抗癌藥物艾黴素包覆於液胞內，包覆量達45 wt%。於酸性環境下(pH 4.68)，艾黴素分子可被釋放於水相中；於中性環境下(pH 7.4)，艾黴素分子的釋放速率則有效被抑制。最後，由體外細胞實驗證實，修飾半乳糖之高分子液胞(無包覆艾黴素)具有良好的細胞存活率；修飾半乳糖之高分子液胞(包覆艾黴素)則有效降低腫瘤細胞(人類肝癌細胞HepG2 cells)存活率。
本研究第三部份是合成羧基-甲基化幾丁聚醣接枝聚苯基穀胺酸高分子，並評估其作為藥物載體或包覆體之可行性。由元素分析及一級氫譜結果顯示，聚苯基穀胺酸於側鏈的聚合度受到進料比的影響。隨著聚苯基穀胺酸長度增加(聚合度增加)，聚苯基穀胺酸的二級結構由β-摺疊結構轉變為α-螺旋結構。羧基-甲基化幾丁聚醣接枝聚苯基穀胺酸高分子經由二次乳化程序可得到高分子液胞結構。螢光實驗結果顯示，低分子量螢光物有較高的釋放速率，主要是低分子量螢光物經由擴散程序釋放至水相中；反之，高分子量螢光物釋放速率則有效被抑制(經過300小時約釋放20%)。上述結果顯示，羧基-甲基化幾丁聚醣接枝聚苯基穀胺酸高分子液胞具極大潛力應用於生醫領域(如藥物傳遞或蛋白質包覆)。

In the recent year, the development of functional polymer nanoparticles has received a great attraction, due to their versatile nanostructure and potential applications in biomedicine. The aim of this work is to develop glycopolypeptides and evaluate their feasibility in biomedical applications. First of all we showed the synthesis, self-assembly behavior, and feasibility of the amphiphilic polypeptides, poly(L-lysine)-g-hexanoyl (PLH) for protein encapsulation. The self-assembly behavior of PLH polymers in aqueous solution can be controlled by the changes in the substitution of hexanoyl groups and chain conformation. The polymers were found to form vesicular structures in aqueous solutions, and their particle sizes and chain conformation can be tuned by the change in respond to the external pH. The oxygen protein, myoglobin (Mb), can be loaded into the aqueous compartment of the vesicles. Further, the Mb-loaded vesicles can be stabilized via genipin-crosslink, as indicated by the stable vesicular structure in acidic condition. The conjugation of lactobionolactone, a modal targeted ligand to HepG2 cells, onto the PLH polymers was performed. The glycopolypeptide vesicles were employed for drug encapsulation, i.e. doxorubicin (DOX). Upon a pH gradient between the outside and inside of vesicles, a high DOX loading level (45 wt%) can be achieved. The crosslinked, vesicles loaded with DOX exhibited noticeable pH-sensitive behavior with accelerated DOX release at acidic condition in comparison with the retarded drug release at pH 7.4. The release rate can also be controlled by the genipin to amine feed ratio. The cytocompatibility of the polypeptides was improved upon grafting the saccharide group and crosslink. The DOX-loaded vesicles exhibited a comparable cytotoxicity with respect to free DOX against HepG2 cells.
Another type of amphiphilic glycopolypeptides, carboxymethyl chitosan-graft- poly(γ-benzyl-glutamate) (m-Chi-g-PBLG), were synthesized and their feasibility in biomedical application was evaluated. The m-Chi-g-PBLG was prepared through ring-opening polymerization of γ-benzyl-L-glutamate N-carboxyanhydride (NCA) using short chained m-Chi as the macroinitiator and the as-prepared glycopolypeptides were employed to form vesicles in aqueous solution. The elemental and NMR analyses revealed that the polymerization degree (DP) of grafted PBLG could be tuned by varying the feed ratio of NCA to m-Chi. The conformation of the grafted PBLG chains transformed from β-sheet to α-helix was correlated with the PBLG chain length. The m-Chi-g-PBLG vesicles can be prepared using double emulsion method and their sizes can be adjusted between 140 and 250 nm. Based on the result of fluorescence measurement, the release rate of the loaded FITC-dextran from vesicles increased with decreasing the molecular weight of FITC-dextran. A sustained release of high-molecular-weight FITC-dextran for a time period over two weeks can be achieved.

Contents
Abstract……………………………………………………………………………I
摘要………………………………………………………………………………III
致謝........................................................................................................................V
Contents………………………………………………………………………..VI
List of Tables........................................................................................................... IX
List of Schemes.....................................................................................................XI
List of Figures........................................................................................................XII
Chapter 1. Introduction
1.1 Background...................................................................................................1
1.2Research motivation……………………………………………………….2
Chapter 2. Literature review
2.1 Polypeptides……………………………………………………………….2
2.2 Glycopolypeptides…………………………………………………..…….6
2.3 Polymeric Vesicle…………………………………………………………7
Ch3. Experimental Section
3.1 Materials…………………………………………………………………..9
3.2 Synthesis of copolypeptides……………………………………………….9
3.2.1 Synthesis of poly(L-lysine)-g-hexanoyl (PLH) and poly(L-lysine)-
g-hexanoyl-g-lactobionolactone (PLHG)………………………………….9
3.2.2 Synthsis of Carboxylmethyl chitosan-g-poly(γ-benzyl-L-Glutamate) (m-Chi-g-PBLG)…………………………………….……………..12
3.3 Preparation of polymer vesicles………………………………….……….13 
3.3.1 Preparation of PLH/PLHG and m-Chi-g-PBLG vesicles.........................13
3.3.2 Critical aggregation concentration (cac) measurements…………....14
3.4 Application as drugs carriers………………………………………..…….14
3.4.1 Preparation of PLH/PLHG vesicles and cross-linked by genipin.....14
3.4.2 Encapsulated Mb and cross-linked PLH vesicles by genipin……….15
3.4.3 Loading of doxorubicin (Dox) in the PLHG vesicles and in vitro Dox release............................................................................................................…16
3.4.4 Cytotoxicity assay of Dox-loaded PLH/PLHG vesicles……….......17
3.4.5 Loading of FITC-dextran in the m-Chi-g-PBLG vesicles and in vitro FITC-dextran release………………………………..…………….18
3.5 Characterization and Sample Measurements…………………………….18
 Chapter 4. Alkyl Chain Grafted Poly(L-lysine): Self-Assembly and Biomedical Application as Carriers
4.1 Synthesis and characterization of PLH........................................................21
4.2 Self-assembly of PLH copolypeptides.........................................................25
4.3 CD analysis.................................................................................................30
4.4 NMR and titration analysis..........................................................................35
4.5 Encapsulation of Myoglobin in the PLH vesicles……...............................38
4.6. Crosslinking of Mb-loaded PLH particles………........……......................43
Chapter 5. Bioactive vesicles from saccharide- and hexanoyl- modified poly(L-lysine) copolypeptides and evaluation of the cross-linked vesicles as carriers of doxorubicin for controlled drug release
5.1. Synthesis and characterization of amphiphilic copolypeptides………......46
5.2 Self-assembly of PLH/PLHG copolypeptides……………………………..51
5.3 Chain conformation of amphiphilic PLH and PLHG copolypeptides........57
5.4 Drug loading and in vitro release…………………....................................62
5.5 Cytotoxicity test……………………………………………………………71
Chapter 6. Carboxylmethyl Chitosan-graft-poly(γ-benzyl-L- glutamate) Glycopeptides: Synthesis and Particle Formation as Encapsulants
6.1 Synthesis and characterizaton of m-Chi-g-PBLG. ………….......................73
6.2 Conformational and Structural analysis. …………………………………...81
6.2.1 Thermal analysis………………………………………………….….81
6.2.2 FTIR measurement...............................................................................83
6.2.3 Solid state 13C NMR analysis…………………………………………85
6.2.4 X-ray diffraction (XRD) and wide-angle X-ray diffraction (WAXD) measurements……………………………………………….…88
6.3 Particle Formation. ……………………………………………………….91
6.4 Encapsulation and Release of FITC-dextran. …..................………........104
Chapter 7 Conclusions................................................................................107
List of publications…………………………………………………………109
Chapter 8. Reference………………………………………………………110

List of Tables
Chapter 4
Table 4-1 Characterization of self-assembled PLH vesicles prepared at pH 7.4 in PBS and estimation of substitution degree by 1H NMR………….25
Table 4-2 The percentages of different secondary conformations adopted by PLH at different pH...………………………….................................…….34
Table 4-3 Characterization of Mb-loaded PLH particles………………………...39
Chapter 5
Table 5-1. Characterization of self-assembled K192-g-Hex72 and K192-g-Hex72-g- Lac30 copolypeptides in PBS (pH 7.4, I=0.01 N)…………….…50
Table 5-2. Average hydrodynamic radius (<Rh>) and  polydispersity index (PDI) of supramolecular structures formed by K192-g-Hex72 and K192-g-Hex72-g- Lac30 in PBS (pH 7.4)..........................................................................53
Table 5-3. Light scattering (LS) results of supramolecular structures formed by K192-g-Hex72 and K192-g-Hex72-g-Lac30 in PBS (pH 7.4, I= 0.01 N)………………………………………………………………….57
Table 5-4. The relative percentages of different secondary conformations adopted by K192, K192-g-Hex72, and K192-g-Hex72-g-Lac30 at different conditions…………………………………………………………...61
Table 5-5. The encapsulation efficiency and loading capacity of K192-g-Hex72-g- Lac30 vesicles prepared at different Dox concentrations…………….67
Table 5-6. Kinetic data calculated from in vitro drug-release profiles………….70
Chapter 6
Table 6-1. The calculated average graft degree (DP) of PBLG in different copolymers from 1H NMR, EA, and GPC……………………….…78
Table 6- 2. Characterization of m-Chi-g-PBLG18 vesicles without PEG-NH2….95
Table 6-3. Characterization of m-Chi-g-PBLG vesicles at 0.2 DMSO/CH2Cl2 solvent ratio with 15 wt% PEG-NH2……………………………….99
Table 6-4. Characterization of m-Chi-PBLG57 vesicles at 0.2 DMSO/CH2Cl2 solvent ratio with different weight percentages of PEG-NH2 at pH 7.4………………………………………………………………..…..102
Table 6-5. Characterization of FITC-dextran-loaded m-Chi-PBLG18 particles and summary of fitting constants, apparent diffusivity and half life t50, for cumulative release……………………………………………………...106

 
List of Schemes
Chapter 2
Scheme 2 1. Synthesis of NCAs. ………………………………………….……..4
Scheme 2 2. Initiation of ring-opening polymerization of NCAs by primary amine…………………………………………………………….4
Scheme 2 3. Initiation of ring-opening polymerization of NCAs by transition metal…………………………………………………………....4
Chapter 3
Scheme 3-1. Synthetic strategy for poly(L-lysine)-graft-hexanoyl (PLH)…..11
Scheme 3-2. Synthetic strategy for poly(L-lysine)-graft-hexanoyl- lactobionolactone (PLHG)…………...........................................11 
Scheme 3-3. Synthesis scheme of m-Chi-g-PBLG copolymers…………………13






List of Figures
Chapter 2
Figure 2-1. Scheme of the formation of the three different secondary structures α-helix, β-sheet and random coil ………………………………..….5
Figure 2-2. Schematics of block copolymer fractions with respective cryogenic transmission electron microscopy images showing vesicles or worm micelles and spherical micelles………………………....................8
Chapter 4
Figure 4-1. The GPC chromatograms of Lys260 (Mn=68900, Mw/Mn= 1.25, top) and Lys190 (Mn=51900, Mw/Mn= 1.19, bottom)………..………21
Figure 4-1. The GPC chromatograms of Lys260 (Mn=68900, Mw/Mn= 1.25, top) and Lys190 (Mn=51900, Mw/Mn= 1.19, bottom)…………………22
Figure 4-2. 1H NMR spectra of (A) K260-g-Hex26, (B) K260-g-Hex100, and (C) K260-g-Hex180 in CD3OD…………………………………………23
Figure 4-3. 1H NMR spectra of (A) K190-g-Hex20, (B) K190-g-Hex70 and (C) K190-g-Hex130 in CD3OD……………………….…………………24
Figure 4-4. The hydrodynamic diameter distributions for 2 mg/ml buffer solution (I=0.01 N) of K260-g-Hex100 with different ionic strengths.............27
Figure 4-5. The hydrodynamic diameter distributions for PLH assemblies in PBS (pH 7.4, I=0.01 N)…………………………………………..……..28
Figure 4-6. TEM image of vesicles formed from (A) K190-g-Hex70 and (B) K260-g-Hex26 (C) K190-g-Hex130 and (D) K260-g-Hex100copolypeptide at pH 7.4 in PBS using positive staining RuO4.............................29
Figure 4-7. CD spectra obtained for 2 mg/ml buffer solution of K260-g-Hex100 at different ionic strengths…………………………………………….31
Figure 4-8. CD spectra obtained for (A) K260, (B) K260-g-Hex26, (C) K260-g-Hex100; (D) K260-g-Hex180, at pH 4.68 (■), 7.4 (□), and 10.0 (▲), respectively........................................................................32
Figure. 4-9 CD spectra obtained for (A) K190, (B) K190-G-Hex20, (C) K190-G-Hex70, and (D) K190-G-Hex130 copolypeptides at pH 4.68 (■), 7.4 (□), and 10.0 (▲), respectively………………………………………….33
Figure 4-10. 1H NMR spectra of K190-G-HEX130 copolypeptide in D2O at (A) pH 4.7 (B) pH 7.4 (C) pH 10.0………………………………….36
Figure 4-11. Apparent dissociation constant as a function of degree of ionization for (A) K260 series and (B) K190 series................................37
Figure 4-12. TEM images of (A) Mb-loaded K190-g-Hex20 particles, (B) Mbloaded K260-g-Hex26 particles, (C) Mb-loaded K190-g-Hex70 particles, and (D) Mb-loaded K190-g-Hex130 particles…………………………………40
Figure 4-13. Adsorption spectra of (A) Mb-loaded K260-g-Hex26 particle solution, and (B) Mb-loaded K190-g-Hex20 particle solution after reduction and further introduction of O2 gas……………………………………41
Figure 4-14. Change in the absorbance at 434 nm ofthe Mb-loaded PLH vesicles by the alternating introduction of O2 gas to Ar the solution…………….42
Figure 4-15. (A) UV-vis spectra of K190-g-Hex70 vesicles crosslinked by genipin as a function of time at pH 5 and (B) TEM image of crosslinked K190-g-Hex70 vesicles. The sample was prepared at pH 5 in DI water..............................................................................................…44
Figure 4-16. The hydrodynamic diameter distributions, f(Dh), for crosslinked Mb-loaded PLH particles…………………….………………….45
Figure 4-17. TEM images of (A) crosslinked Mb-loaded K260-g-Hex100 particles and (B) crosslinked Mb-loaded K190-g-Hex70 particles using genipin…….45
Chapter 5
Figure 5-1. The GPC chromatograms of Lys192 (Mn=50340, Mw/Mn= 1.14) from three detectors (RI, right angle light scattering, and viscometer). …48
Figure 5-2. 1H NMR spectra of (a) K192, (b) K192-g-Hex72, and (c) K192-g-Hex72-g-Lac30 in CD3OD. Pyridzine was used as an internal standard compound (8.26 ppm)…………………….………….49
Figure 5-3. FT-IR spectra of (a) K192, (b) K192-g-Hex72, and (c) K192-g-Hex72-g-Lac30 copolypeptides…………………………50
Figure 5-4. TEM images of aggregates self-assembled from (a) K192-g-Hex72 and (b) K192-g-Hex72-g-Lac30 in PBS (0.01N, pH 7.4). …………………….53
Figure 5-5. Size distribution of the vesicles formed at (a) I = 0.01N (b) I = 0.15N.............................................................................................54 
Figure 5-6. Berry plots of aggregates self-assembled from (a) K192-g-Hex72 and (b) K192-g-Hex72-g-Lac30 by dialysis method in PBS (pH 7.4, I=0.01N)…………………………………………………..……..55
Figure 5-7. The dn/dc data of K192-g-Hex72 (top) and K192-g-Hex72-g-Lac30 (bottom) prepared in PBS (pH 7.4, I= 0.01 N)…………….……………….….56
Figure 5-8. CD spectra of self-assembled (a) K192, (b) K192-g-Hex72, and (c) K192-g-Hex72-g-Lac30 in PBS buffer (0.15N) at pH 4.68 (■), 7.4 (□), and 10.0 (▲), respectively………………………………..……..60
Figure 5-9. Hydrodynamic radii of K192-g-Hex72-g-Lac30 vesicles and Doxloaded
K192-g-Hex72-g-Lac30 vesicles in PBS under different loading conditions as a function of genipin to amine feed ratio (R)…………………..…68
Figure 5-10. TEM images of (a) Dox-loaded K192-g-Hex72 vesicles and (b) Dox-loaded K192-g-Hex72-g-Lac30 vesicles cross-linked by genipin in PBS (pH 7.4, 0.15 N). The value of R is 0.25.……………….…..68
Figure 5-11. Cumulative release of Dox-loaded cross-linked K192-g-Hex72-g-Lac30 vesicles at different genepin to amine feed ratios in PBS (ionic strength 0.15 N) at 37 oC. The open and solid symbols represent the release experiments conducted at pH 4.68 and 7.4, respectively……………69
Figure 5-12. Drug released profiles of doxorubicin-loaded K192-g-Hex72 and K192-g-Hex72-g-Lac30 vesicles in PBS (I=0.15N) at 37 oC. ………69
Figure 5-13. Cytotoxicity of Hep-G2 cells treated by K192, K192-g-Hex72, and cross-linked K192-g-Hex72-g-Lac30 with R=0.0625, 0.125, and 0.25 as a function of polypeptide concentration…………………..….….72
Figure 5-14. Cytotoxicity of Hep-G2 cells treated by free Dox and Dox-loaded cross-linked K192-g-Hex72-g-Lac30 with R=0.125 and 0.25 at the dose of 10 and 25 g/mL………………………………………………72

Chapter 6
Figure 6-1. 1H NMR spectra of m-Chi and m-Chi-g-PBLG57 in CF3COOD......76
Figure 6-2. 1H NMR spectra of m-Chi-PBLG6, m-Chi-PBLG11, m-Chi-PBLG14, and m-Chi-PBLG18 in TFA-d1……………………………………….…77
Figure 6-3. GPC chromatograms (refractive, viscosity, and UV index detector signals) of (from top to bottom) m-Chi-PBLG11, m-Chi-PBLG14, m-Chi-PBLG18, and m-Chi-PBLG57 graft copolymers……………..80
Figure 6-4. DSC thermograms of (a) m-Chi and (b) m-Chi-g-PBLG57………….82
Figure 6-5. DSC thermograms of m-Chi-g-PBLG graft copolymers during the second heating run……………………………………………..…..83
Figure 6-6. FTIR spectra of  (a) m-Chi-g-PBLG6, (b) m-Chi-g-PBLG11, (c) m-Chi-g-PBLG14, (d) m-Chi-g-PBLG18, and (e) m-Chi-g-PBLG57…85
Figure 6-7. 13C NMR spectra of  (a) m-Chi-g-PBLG6, (b) m-Chi-g-PBLG11, (c) m-Chi-g-PBLG14, (d) m-Chi-g-PBLG18, and (e) m-Chi-g-PBLG57..87
Figure 6-8. X-ray diffraction (XRD) patterns of (a) m-Chi, (b) m-Chi-g-PBLG6, (c) m-Chi-g-PBLG11, (d) m-Chi-g-PBLG14, (e) m-Chi-g-PBLG18, and (f) m-Chi-g-PBLG57 at room temperature……………………………...89
Figure 6-9. WAXS patterns of m-Chi-g-PBLG57 at 50, 100, and 150 oC……….90
Figure 6-10. WAXD patterns of (a) m-Chi-g-PBLG6, (b) m-Chi-g-PBLG11, (c) m-Chi-PBLG14, and (d) m-Chi-PBLG18 at 50, 100, and 150 oC….91
Figure 6-11. (a) The size distribution of m-Chi-g-PBLG18 vesicles without PEG-NH2 and (b) TEM image of the vesicles ( R＝0.2 )…………96
Figure 6-12. (a) Berry Plot and (b) TEM image of m-Chi-g-PBLG18 vesicles ( R＝0.5 ) without PEG-NH2. ………………………………97
Figure 6-13. (a) 1H NMR spectra of m-Chi-PBLG57 in TFA-d1 and (b) 1H NMR spectra of m-Chi-PBLG57 particles in D2O / CD3SOCD3 (V/V, 4/1)………….98
Figure 6-14. (a) Berry Plot of the m-Chi-g-PBLG vesicles with 15 wt% of PEG-NH2 and (b) size distribution of m-Chi-g-PBLG57 vesicles with different content of PEG-NH2……………………………………..100
Figure 6-15. TEM images of (a) m-Chi-g-PBLG6, (b) m-Chi-g-PBLG11, (c) m-Chi-g-PBLG14, and (d) m-Chi-g-PBLG18 vesicles. The vesicles were prepared by double emulsion method with 15 wt% of PEG-NH2………………………………………………………..101
Figure 6-16. (a) Berry Plot of m-Chi-g-PBLG57 vesicles with different content of PEG-NH2 and TEM images of the m-Chi-g-PBLG57 vesicles with (b) 0 wt% and (c)15 wt% of PEG-NH2………………………………..102
Figure 6-17. TEM image of the m-Chi-g-PBLG57 vesicles with different contents of PEG-NH2 (a) 5 %, (b) 10 %........................................................103
Figure 6-18. varible molecular weight of FITC-dextran release profiles of  loaded m-Chi-g-PBLG18 vesicles in phosphate buffer (I=0.15N) at 37 oC until 540 hr………………………………………………………….106

                                    

Chapter 8. Reference.
1. Fung, S. Y., Duhamel, J. and Chen, P. J. Phys. Chem. A. 2006, 110, 11446– 11454.
2. Hu, Z. G., Fan, X. S., Wang, H. J. and Wang, J. J. Polymer. 2009, 50 (17), 4175–4181.
3. Huang,C. C., Su,C. H., Li,W. M., Liu,T. Y., Chen, J. H. and Yeh, C. S. Adv. Funct. Mater. 2009, 19, 249–258.
4. Kamiya,S., Yamada, M., Kurita,T., Miyagishima,A., Arakawa, M. and Sonobe,T. Int. J. Pharm. 2008, 354, 242–247.
5. Carlsen, A., Lecommandoux, S. Curr. Opin. Colloid Interface Sci. 2009, 14, 329-339
6. Antonietti, M., Förster, S. Adv Mater. 2003,15,1323–33.
7. Choucair, A., Eisenberg, A. Eur Phys J E Soft Matter. 2003, 10, 37–44.
8. Discher, B.M.,Won, Y.Y., Ege, D.S., Lee, J., Bates, F.S., Discher, D.E., Science .1999,284,1143.
9.Discher, D.E., Eisenberg, A. Science. 2002, 297, 967–973.
10. Taubert, A., Napoli, A., Meier, W. Curr Opin Chem Biol. 2004,8,598–603.
11. Dong,C. M., Sun, X. L., Faucher,K. M., Apkarian R. P. and Chaikof, E. L. Biomacromolecules. 2004, 5, 224.
12. Schatz, C., Louguet,S., Le Meins J. F. and Lecommandoux, S. Angew. Chem. Int. Ed.2009, 48, 2572.
13. Upadhyay,K. K., Le Meins,J. F., Misra, A., Voisin,P., Bouchaud,V., Ibarboure,E., Schatz C. and Lecommandoux, S. Biomacromolecules. 2009, 10, 2802.
14. Lis, H., Sharon, N. Chem. Rev. 1998, 98, 637–674
15. Deming, T. J., Nature 1997, 390, 386.
16. Kricheldorf, H. R., Angew. Chem. Int. Ed. 2006, 45, 5752.
17. Habraken, G. J. M., Heise, A., Thornton, P. D., Macromol. Rapid Commun. 2011, 33, 272.
18. He, C., Zhuang, X., Tang, Z., Tian, H., Chen, X., Adv. Healthcare Mater. 2012, 1, 48.
19. Dimitrov, I. and Schlaad, H., Chem. Commun. 2003, 2944.
20. Sanjoh, M., Hiki, S., Lee, Y., Oba, M., Miyata, K., Ishii, T., Kataoka, K., Macromol. Rapid Commun. 2010, 31, 1181.
21. Takae, S., Miyata, K., Oba, M., Ishii, T., Nishiyama, N., Itaka, K., Yamasaki, Y.,Koyama, H., and Kataoka, K., J. Am. Chem. Soc. 2008, 130, 6001.
22. Han, M., Bae, Y., Nishiyama, N., Oba, K. M. M., and Kataoka, K., J. Control. Release 2007, 121, 38.
23. Kataoka, K., Harada, A., and Nagasaki, Y., Adv. Drug Deliv. Rev. 2001, 47, 2944.
24. Hamaguchi, T., Matsumura, Y., Suzuki, M., Shimizu, K., Goda, R., Nakamura, I., Nakatomi, I., Yokoyama, M., Kataoka, K., and Kakizoe, T., Br. J Cancer 2005, 92, 1240.
25. Malcher, M., Volodkin, D., Heurtault, B., André, P., Schaaf, P., Möhwald, H., Voegel, J.-C., Sokolowski, A., Ball, V., Boulmedais F., and Frisch, B., Langmuir, 2008, 24, 10209.
26. Xu, N., Du, F.-S., and Li, Z.-C., J. Polym. Sci. Part A 2007, 45, 1889.
27. Maruyama, A., Ishihara, T., Kim, J.-S., Kim, S. W., and Akaike T., Bioconjugate Chem. 1997, 8, 735.
28. Lai, J.-K., Chuang, T.-H., Jan, J.-S., Wang, S. S.-S., Colloid Surf. B: Biointerfaces 2010, 80, 51.
29. Gaspard, J.; Silas, J. A.; Shantz, D. F.; Jan, J.-S. Supramol. Chem. 2010, 22, 178.
30. Jan, J.-S., Chuang, T.-H., Chen, P.-J., Teng, H., Langmuir 2011, 27, 2834.
31. Huang, Y.-C., Yang, Y.-S., Lai, T.-Y., Jan, J.-S., Polymer 2012, 53, 913.
32. Huang, Y.-C., Arham, M., Jan, J.-S. Soft Matter 2011, 7, 3975.
33. Huang, Y.-C., Arham, M., Jan, J.-S., Euro. Polym. J. 2013, 49, 726–737
34.Wen, W.-S., Lai, J.-K., Lin, Y.-J., Lai, C.-M., Huang, Y.-C., Wang, S. S.-S., Jan, J.-S., Biopolymers, 2012, 97, 107.
35. Jan, J.-S., Chen,P.-S., Hsieh, P.-L., Chen, B.-Y. ACS Appl. Mater. Interface .2012 , 4, 6865-6874.
36. Choi, S. W., Makita, N., Inoue, S., Lesoil,C., Yamayoshi, A., Kano, A., Akaike, T., and Maruyama, A., Nano Lett. 2007, 7, 172.
37. Lee, E. S., Kim, D., Youn, Y. S., Oh, K. T., and Bae, Y. H., Angew. Chem. Int. Ed. 2008, 47, 2418.
38. Miura, Y., J. Polym. Sci. Part A: polym. Chem. 2007, 45, 5031.
39. Daly, W. H., Poche D. Tetrahedron Letters.1988, 29, 5859-5862.
40. Deming, T.J. Journal of Polymer Science Part a-Polymer Chemistry. 2000, 38, 3011-3018.

41. Deming, T.J. Advanced Materials. 1997, 9, 299-305.
42. Hermel, H., Miller, R. Colloid Polym Sci .1995, 273, 387.
43. Lee, E.S., Kim, D., Youn, Y.S., Oh, K.T., Bae, Y.H. Angew Chem Int Ed . 2008, 47, 2418-2421.
44. Mosmann, T.J. Immunol Methods. 1983, 65, 55-63.
45.Slater, T.F., Sawyer, B., Strauli, U. Biochim Biophys Acta. 1963, 77, 383-393.
46. Deming, T.J. Prog Polym Sci. 2007, 32, 858-875.
47. Yu, H., Chen, X., Lu, T., Sun, J., Tian, H., Hu, J., Wang, Y., Zhang, P. and Jing, X. Biomacromolecules. 2007, 8, 1425-1435
48. Kramer, J., Deming, T.J. J Am Chem Soc. 2010, 132, 15068-15071.
49. Stoehr, T., Blaudszum, A.-R., Steinfeld, U., Wenz, G. Polym Chem. 2011, 2, 2239-2248.
50. Won, Y.-Y., Davis, H.T., Bates, F.S. Science. 1999, 283, 60-63.
51. Stewart, S., Liu, G. Chem Mater. 1999,11 ,1048-1054.
52. Armes, S.P. J Am Chem Soc. 1998, 20,12135-12136.
53. Checot, F., Lecommandoux, S., Gnanou, Y., Klok, H.A. Angew Chem Int Ed. 2002, 41, 1339-1343.
54. Checot, F., Lecommandoux, S., Klok, H.A., Gnanou, Y. Eur Phys JE 2003, 10, 25-35.
55. Loomis, K., McNeeley, K., Bellamkonda, R.V. Soft Matter. 2010, 7, 839-856.
56. Li, L., Wang, H., Ong, Z.Y., Xu, K., Ee, P.L.R., Zheng, S., Hedrick, J.L., Yang, Y.-Y. Nano Today. 2010, 5, 296-312.
57. Narin, R., Armes, S.P. Biomacromolecules. 2003, 4, 1746-1758.
58. Wang, R., Xu, N. Du, F.-S. Li, Z.-C. Chem Commun. 2010, 46, 3902-3904.
59. Discher, D.E., Ahmed, F. Annual Review of Biomedical Engineering .2006, 8, 323.
60. Choi, S.W., Makita, N., Inoue, S., Lesoil, C., Yamayoshi, A., Kano, A., Akaike, T. and Maruyama, A. NANO LETTERS. 2007, 7, 172-178.
61. Jiang, G.-B., Quan, D., Liao, K., Wang, H. Carbohydrate Polymers. 2006, 66, 514-520.
62. Schmaljohann, D. Adv. Drug Delivery Rev. 2006, 8, 323-341
63. Checot, F., Lecommandoux, S., Klok, H.-A., Gnanou, Y. Eur. Phys. J. E. 2003, 10, 25-35
64. Checot, F., Rodriguez-Hernandez,J., Lecommandoux, S., Gnanou,Y. Biomol. Eng. 2007, 24, 81-85
65. Du, J. Z., Tang,Y. P., Lewis, A. L., Armes,S. P. J. Am. Chem. Soc. 2005, 127, 17982-17983
66. Bellomo, E. G., Wyrsta, M. D., Pakstis,L. D., Pochan, J., Deming,T. J. Nat. Mater. 2004, 3, 244-248.
67. Holowka, E. P., Sun, V. Z., Kamei, D. T., Deming,T. J. Nat. Mater. 2007, 6, 52-57.
68. Narin, R., Armes, S.P. Biomacromolecules. 2003, 4, 1746-1758.
69. Liu, T.-Y., Chen, S.-Y., Lin, Y.L., Liu, D.-M. Langmuir. 2006, 22, 9740.
70. Freytag, T., Dashevsky, A., Tillman, L., Hardee, G.E., Bodmeier, R.J. J Controlled Release. 2000, 69, 197.
71. Chu, B. In Laser Light Scattering, 2nd ed, Academic Press, New York 1991.
72. Bradburry, E. M., Robinson, C.C., Goldman, H. and Rattle, H. W. E. Biopolym., 1968, 6, 851-862.
73. Harada, A., Cammas, S. and K. Kataoka, Macromolecules, 1996, 29, 6183-6188.
74. Triftaridou, A. I., Checot, F. and Iliopoulos, I. Macromolecular Chem. Phys., 2010, 211, 768-777.
75. Kukula, H., Schlaad, H., Antonietti, M. and Foerster, S. J. Am. Chem. Soc, 2002, 124, 1658-1663.
76. Kruijff, B. D., Rietveld, A., Telders, N. and Vaandrager, B. Biochim Biophys. Acta, 1985, 820, 295-304.
77. Rao, J., Zhang, Y., Zhang J. and Liu, S. Biomacromolecules, 2008, 9, 2586-2593.
78. Kishimura, A., Koide,A., Osada, K., Yamasaki, Y. and Kataoka, K. Angew. Chem. Int. Ed., 2007, 46, 6085-6088.
79. Kent, M. S., Yim, H. and Sasaki, D. Y. Langmuir, 2002, 18, 3754-3757.
80. Yuan, Y., Chesnutt, B. M., Utturkar,G., Haggard, W. O., Yang,Y. J. , Ong, L. and Bumgardner, J. D. Carbohydrate Polym., 2007, 68, 561-567.
81. Kaminski, K., Zazakowny, K., Szczubialka, K. and Nowakowaska, M. Biomacromolecules, 2008, 9, 3127-3132.
82. Mi, F.-L., Shyu, S.-S. and Peng, C.-K. J. of Polym. Sci. Part A: Polym. Chem., 2005, 43, 1985-2000.
83. Meena, R., Prasad, K. and Siddhanta, A. K. J. of Appl. Polym. Sci., 2007, 45, 1889-1898.
84. Liu, T.-Y. and Lin, Y.-L. Acta Biomater., 2010, 6, 1423-1429.
85. Wu, C., Li, M., Kwan, S., Liu, G. Macromolecules. 1998, 31, 7553-7554.
86. Vagberg, L.J.M., Cogan, K.A., Gast, A.P. Macromolecules. 1991, 24, 1670-1677.
87. Jan, J.-S., Shantz, D.F. Adv Mater. 2007, 19, 2951-2956.
88. Ahmed, F., Pakunlu, R.I., Brannan, A., Bates, F., Minko, T., Discher, D.E., Journal of Controlled Release. 2006,116 ,150-158.
89. Choucair, A., Lim Soo, P., Eisenberg, A. Langmuir. 2005, 21, 9308-9313.
90. Kwon, G., Naito, M., Yokoyama, M., Okano, T., Sakurai, Y., Kataoka, K., Journal of Controlled Release. 1997, 48, 195-201.
91. Allen, C., Han, J., Yu, Y., Maysinger, D., Eisenberg, A. Journal of Controlled Release. 2000, 63, 275-286.
92. Hagan, S.A., Coombes, A.G.A., Garnett, M.C., Dunn, S.E., Davies, M.C., Illum, L., Davis, S.S., Harding, S.E., Purkiss, S., Gellert, P.R. Langmuir. 1996, 12 , 2153-2161.
93. Sanson, C., Schatz, C., Le Meins, J.-F., Soum, A., Thevenot, J., Garanger, E., Lecommandoux, S. Journal of Controlled Release. 2010, 147, 428-435.
94. Kim, J.O., Kabanov, A.V., Bronich, T.K. Journal of Controlled Release. 2009, 138, 197-204.
95. Ritger, P.L., Peppas, N.A. Journal of Controlled Release. 1987, 5, 23-36.
96. Lee, Y., Park, S. Y., Mok, H., Park,T. G. Bioconjugate Chem. 2008, 19, 525–531.
97. Watanaba, J., Ichitaro, U. Polymer. 1984, 25, 1711.
98. Papadopoulos, P., Floudas, G., Klok, H.A., Schnell, I., Pakula, T. Biomacromolecule. 2004, 5, 81.
99. Kuo, S.-W., Tsai, H.-T. Polymer. 2010, 51, 5695.
100. Wan, Y., Wu, H., Yu, A.X., Wen, D.J. Biomacromolecules. 2006, 7, 1362.
101. Murata, K., Katoh, E., Kuroki, S., Ando, I. J Mol Struct. 2004, 689, 223.
102. Lecommandoux, A., Achard, M.F., Langenwalter, J.F., Klok, H.A. Macromolecules. 2001, 34, 9100.
103. Floudas, G., Papadopoulos, P., Klok, H.A., Vandermeulen, G.W.M., Rodriguez- Hernandez, J. Macromolecules .2003, 36, 3673.
104. Hellaye, Le., Fortin, M., Guilloteau, N., Soum, J., Lecommandoux, A., Guillaume, S.M. Biomacromolecules. 2008, 9, 1924.
105. Minich, E.A., Nowak, A.P., Deming, T.J., Pochan, D.J. Polymer. 2004, 45, 1951.
106. Sun, J., Chen, X., Deng, C., Yu, H., Xie, Z., Jing, X. Langmuir . 2007, 23, 8308.
107. Chiang, W.-H., Lan, Y.-J., Huang, Y.-C., Chen, Y.-W., Huang, Y.-F., Lin, S.-C., Chern, C.-S., Chiu, H.-C. Polymer. 2012, 53, 2233.
108. Leach, J.B., Schmidt, C.E. Biomaterials .2005, 26, 125.
109. Cussler, E.L. Diffusion: Mass Transfer in Fluid Systems; Cambridge University Press. Cambridge. U. K. 2003.
110. Hines, D.J., Kaplan, D.L. Biomacromolecules. 2011, 12, 804.

校內：2018-02-14公開
校外：2018-02-14公開

簡易檢索 / 詳目顯示

相關論文