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系統識別號 U0002-2402202113083400
中文論文名稱 幾丁聚醣/聚(氮-異丙基丙烯醯胺-乙烯胺-氮-羥甲基丙烯醯胺)半互穿網狀水凝膠之製備與應用
英文論文名稱 Preparation of CS/Poly(NiPPAm-co-VAm-co-NMA) Semi-IPN Network Hydrogels and their applications
校院名稱 淡江大學
系所名稱(中) 化學工程與材料工程學系碩士班
系所名稱(英) Department of Chemical and Materials Engineering
學年度 109
學期 1
出版年 110
研究生中文姓名 温惠貽
研究生英文姓名 Hui-Yi Weng
學號 607400024
學位類別 碩士
語文別 中文
口試日期 2021-01-14
論文頁數 147頁
口試委員 指導教授-董崇民
委員-邱文英
委員-糜福龍
中文關鍵字 聚氮-異丙基丙烯醯胺  聚乙烯胺  N-羥甲基丙烯醯胺  自由基聚合法  半互穿型水凝膠 
英文關鍵字 Poly(N-isopropylacrylamide)  Poly(N-vinylamine)  Poly(N-methylolacrylamide)  Free Radical Polymerization  Semi-IPN Network Hydrogels 
學科別分類
中文摘要 本研究利用環境敏感型高分子製備溫度/酸鹼雙重應答之幾丁聚醣/聚(氮-異丙基丙烯醯胺-乙烯胺-氮-羥甲基丙烯醯胺)半互穿型水凝膠。研究中分為三部份來探討,第一部分是利用自由基聚合法合成聚乙烯甲醯胺(Poly(N-vinylforamide), PNVF),探討PNVF在不同的條件下水解成聚乙烯胺(Poly(N-vinylamine), PVAm)之水解率變化。接著,亦是利用自由基聚合法合成P(NP-co-NVF),探討氮-異丙基丙烯醯胺(N-isopropylacrylamide,NP)與NVF單體的進料比例對整體共聚物組成及性質之影響,測其共聚物之溫度/酸鹼敏感性質(最低臨界溶解溫度Lower critical solution temperature, LCST)及顆粒尺寸,進一步添加可熱交聯單體N-羥甲基丙烯醯胺(N-methylolacrylamide, NMA),以自由基聚合法合成P(NP-co-NVF-co-NMA),透過NMA含量不同,測量共聚物LCST之變化。接著利用P(NP-co-NVF-co-NMA)鏈段上NMA的CH2OH基團,加熱使共聚物自交聯,並添加幾丁聚醣(Chitosan, CS)以提高生物相容性,水解熱交聯以形成CS/P(NP-co-VAm-co-NMA)半互穿型水凝膠。利用FTIR對其化學結構進行分析,並探討不同CS與P(NP-co-NVF-co-NMA)之比例對水凝膠之膨潤率、熱性質及表面型態之影響。根據膨潤結果發現,膨潤率隨著NMA含量增加而下降;而在固定NMA含量下,酸性環境(pH=5.5)下的平衡膨潤率大於鹼性環境(pH=7.4),且溫度升高,膨潤率下降,表示成功地合成出具溫度/酸鹼雙重應答之水凝膠。藉由熱性質分析顯示,隨著NMA相對含量的提升,玻璃轉移溫度從112 oC提升至122 oC,有助於增強水凝膠之熱穩定性,並透過SEM證實水凝膠之孔洞隨交聯度提升而變小。
英文摘要 In this study, environmentally sensitive chitosan/poly(N-isopropylacrylamide-vinylamine-N-hydroxymethylacrylamide) semi-interpenetrating network hydrogels with temperature/pH dual response were prepared. This research is divided into three parts to discuss. The first part is the synthesis of poly(vinylformamide) (PNVF) by free radical polymerization, and the study of hydrolysis rate of PNVF to poly(vinylamine) (PVAm) under different conditions. Subsequently, P(NP-co-NVF) was after synthesized by free radical polymerization. The effects of the feeding ratio of N-isopropylacrylamide (NP) to NVF monomer on the overall copolymer composition and properties were investigated, and the temperature/pH responsiveness of the copolymer was measured. By further adding thermal crosslinking monomer N-methylol acrylamide (NMA) with the mutual reaction of the P(NP-co-NVF-co-NMA) copolymer was thus synthesized. The variation of LCST was measured with different contents of NMA in the feed. CH2OH group in NMA on the P(NP-co-NVF-co-NMA) to make the copolymer self-crosslinking, and the addition of chitosan (CS) to improve biocompatibility, hydrolysis and thermal crosslinking occurred simultaneously to form CS/P(NP-co-VAm-co-NMA) semi-IPN hydrogel. FTIR wsa utilized to analyze chemical structure, and the effects of different ratios of CS to P(NP-co-NVF-co-NMA) on the swelling ratio, thermal properties and surface morphology were investigated. According to the swelling data, the swelling ratio decreased with the increase of NMA content. By fixing the NMA content, the equilibrium swelling ratio in an acidic environment (pH=5.5) was greater than that in an alkaline environment (pH=7.4), while it decreased when the temperature was raised, indicating that the hydrogels were responsive to temperature and pH. Moreover glass transfer temperature increasef from 112 oC to 122 oC with the higher content of NMA, which was advantageous for enhancing the thermal stability of the hydrogel. SEM showed that the porosity of the hydrogel decreased with the increase of crosslinking degree.
論文目次 目錄
中文摘要 I
英文摘要 II
目錄 IV
圖目錄 VII
表目錄 XIII
第一章 緒論 1
1.1前言 1
1.2研究動機 2
第二章 文獻回顧 4
2.1幾丁質及幾丁聚醣 4
2.1.1去乙醯度的測定 7
2.1.2幾丁聚醣黏度平均分子量測定 10
2.2環境敏感型高分子 12
2.2.1溫度敏感型高分子 14
2.2.2酸鹼敏感型高分子 18
2.3智慧型水凝膠簡介 21
2.3.1交聯結構水凝膠 23
2.3.2 水凝膠藥物釋放系統 25
第三章 實驗方法與實驗步驟 31
3.1實驗藥品 31
3.2實驗儀器 34
3.3實驗流程圖 37
3.4實驗步驟 39
3.4.1 幾丁聚醣之性質測試 39
3.4.2 PNVF與PVAm之合成與性質測試 42
3.4.3 P(NP-co-NVF)與P(NP-co-VAm)之製備與性質測試 44
3.4.4 P(NP-co-NVF-co-NMA) 之製備與性質測試 46
3.4.5 CS/P(NP-co-VAm-co-NMA)半互穿水凝膠之製備與性質測試 48
3.5結構及性質分析 50
3.5.1官能基結構鑑定(FTIR、NMR) 50
3.5.2粒徑大小及分佈鑑定(DLS) 50
3.5.3最低臨界溶液溫度之(LCST)測定(UV-Vis) 51
3.5.4 膨潤特性 51
3.5.5熱性質分析 (TGA、DSC) 52
3.5.6水凝膠型態分析(SEM) 52
第四章 結果與討論 53
4.1幾丁聚醣之性質測試 53
4.1.1去乙醯度 (Degree of deacetylation,DDA%) 53
4.1.2黏度平均分子量 59
4.1.3幾丁聚醣結構鑑定 (FTIR) 61
4.2 PNVF與PVAm之合成與性質測試 62
4.2.1合成PNVF之結構鑑定(FTIR、NMR) 62
4.2.2由PNVF水解製備PVAm與性質測試 64
4.3 P(NP-co-NVF)與P(NP-co-VAm)之製備與性質測 71
4.3.1自由基聚合法合成P(NP-co-NVF)之結構鑑定(FTIR、NMR) 71
4.3.2 P(NP-co-NVF)之溫感性質(UV-Vis) 75
4.3.3 P(NP-co-NVF)之熱重損失分析 (TGA) 77
4.3.4 P(NP-co-NVF)之玻璃轉移溫度 (DSC) 79
4.3.5 P(NP-co-VAm)之結構鑑定(FTIR、NMR) 80
4.3.6 P(NP-co-VAm)之溫感性質(UV-Vis) 85
4.3.7 P(NP-co-VAm)之粒徑分析(DLS) 88
4.3.8 P(NP-co-VAm)之熱重損失分析 (TGA) 92
4.3.9 P(NP-co-VAm)之玻璃轉移溫度 (DSC) 94
4.4 P(NP-co-NVF-co-NMA) 之製備與性質測試 95
4.4.1 P(NP-co-NVF-co-NMA)之結構鑑定(FTIR、NMR) 95
4.4.2 P(NP-co-NVF-co-NMA)之溫感性質(UV-Vis) 100
4.5 CS/P(NP-co-VAm-co-NMA)半互穿水凝膠之製備與性質測試 103
4.5.1 CS/P(NP-co-VAm-co-NMA)水凝膠之結構鑑定(FTIR) 104
4.5.2 CS/P(NP-co-VAm-co-NMA)水凝膠之膨潤特性 105
4.5.3 CS/P(NP-co-VAm-co-NMA)水凝膠之熱重損失分析 (TGA) 111
4.5.4 CS/P(NP-co-VAm-co-NMA)水凝膠之玻璃轉移溫度 (DSC) 113
4.5.6 CS/P(NP-co-VAm-co-NMA)水凝膠之型態分析(SEM) 114
第五章 結論 134
第六章 建議事項 136
第七章 參考文獻 137


圖目錄
圖1-1 不同劑型之血液中藥物濃度曲線圖 1
圖2-1纖維素結構 4
圖2-2幾丁質結構 4
圖2-3不同排列方式的幾丁質 5
圖2-4幾丁聚醣結構 6
圖2-5 環境刺激時的相對應答行為 12
圖2-6 藥物傳送之刺激響應 13
圖2-7溶液溫度與高分子體積分率()之相變化圖 14
圖2-8 溫度敏感型高分子載體製備及藥物釋放機制示意圖 16
圖2-9 幾丁聚醣-聚(丙烯酸-co-氮異丙基丙烯醯胺)奈米載體示意圖 17
圖2-10 PNVF 酸性水解產生之電子排斥力示意圖 19
圖2-11 智慧型水凝膠對環境產生應答能力 22
圖2-12 化學交聯、物理交聯或雙網絡製備的水凝膠之示意圖 23
圖2-13 (a)Semi-IPNs (b)Full-IPNs合成示意圖 24
圖2-14 藥物釋放系統 25
圖2-15 藥物恆定釋放產生的零級動力學 26
圖2-16 擴散控制系統 26
圖2-17 (a)儲存型系統和(b)基體型系統之載體的幾何形狀 27
圖2-18 膨潤控制系統 29
圖2-19侵蝕控制系統 30
圖3-1 幾丁聚醣純化之流程圖 39
圖3-2 水解裝置示意圖 42
圖3-3 PNVF合成流程圖 43
圖3-4 PNVF不同條件下之水解流程圖 43
圖3-5 自由基聚合法合成P(NP-co-NVF)高分子共聚物流程圖 45
圖3-6 P(NP-co-NVF)之水解流程圖 45
圖3-7自由基聚合法合成P(NP-co-NVF-co-NMA)高分子共聚物流程圖 47
圖3-8 CS/P(NP-co-VAm-co-NMA)水凝膠之流程圖 49
圖4-1幾丁聚醣之H-NMR光譜圖 53
圖4-2幾丁聚醣溶液之導電度與pH值隨加入的NaOH體積變化曲線 54
圖4-3幾丁聚醣溶液之pH值變化曲線一次微分 55
圖4-4不同濃度之N-乙醯基-D-葡萄糖胺一次微分吸光圖 56
圖4-5 N-乙醯基-D-葡萄糖胺一次微分吸光值對濃度之檢量線 57
圖4-6幾丁聚醣紅外線吸收光譜圖 58
圖4-7幾丁聚醣溶液在不同濃度下之還原黏度 (ηred)與固定黏度 (ηinh) 60
圖4-8幾丁聚醣紅外線吸收光譜圖 61
圖4-9自由基聚合法合成之PNVF高分子紅外線光譜圖,起始劑為AIBN,反應溫度60 C,反應時間24小時 62
圖4-10 以自由基聚合法合成之PNVF的NMR圖,起始劑為AIBN,反應溫度60 C,反應時間24小時 63
圖4-11 PNVF水解途徑示意圖 64
圖4-12 PNVF以1 N NaOH(aq)進行40 C水解4小時後的產物之NMR圖 67
圖4-13 PNVF以1 N NaOH(aq)進行40 C水解12小時後的產物之NMR圖 67
圖4-14 PNVF以1 N NaOH(aq)進行80 C水解12小時後的產物之NMR圖 68
圖4-15 PNVF以1 N HCl(aq)進行40 C水解4小時後的產物之NMR圖 68
圖4-16 PNVF以1 N HCl(aq)進行40 C水解12小時後的產物之NMR圖 69
圖4-17 PNVF以1 N HCl(aq)進行80 C水解12小時後的產物之NMR圖 69
圖4-18 PNVF在不同溫度與時間下,以1 N NaOH(aq)進行水解後產物之NMR比較圖 70
圖4-19 PNVF在不同溫度與時間下,以1 N HCl(aq)進行水解後產物之NMR比較圖 70
圖4- 20為自由基聚合法合成的 (a) PNVF、(b) P(NP14-co-NVF)、(c) P(NP19-co-NVF)、(d) P(NP29-co-NVF)以及(e) PNP之FTIR圖 72
圖4-21以自由基聚合法合成之P(NP14-co-NVF)之NMR圖,起始劑為AIBN,反應溫度60 C,反應時間24小時 73
圖4-22以自由基聚合法合成之PNP之NMR圖,起始劑為AIBN, 74
圖4-23以自由基聚合法合成之P(NP19-co-NVF)之NMR圖,起始劑為AIBN,反應溫度60 C,反應時間24小時 74
圖4-24以自由基聚合法合成之P(NP29-co-NVF)之NMR圖,起始劑為AIBN,反應溫度60 C,反應時間24小時 75
圖4-25 PNP與不同P(NP-co-NVF)共聚物在pH7.4下穿透率(λ= 450 nm)對溫度的關係圖(a)及溫度一次微分圖(b),溶液濃度為0.1 % (w/v) 76
圖4-26不同組成之P(NP-co-NVF)的熱重損失圖 78
圖4-27不同組成之P(NP-co-NVF)的熱重損失圖 78
圖4-28不同P(NP-co-NVF)比例之共聚物的DSC二次升溫曲線圖 79
圖4-29 (a)以自由基聚合法合成的P(NP14-co-NVF);(b)P(NP14-co-NVF)以1 N HCl(aq)進行80 C水解12小時後的產物P(NP14-co-VAm)之FTIR圖 81
圖4-30 (a)以自由基聚合法合成的P(NP19-co-NVF);(b)P(NP19-co-NVF)以1 N HCl(aq)進行80 C水解12小時後的產物P(NP19-co-VAm)之FTIR圖 81
圖4-31 (a)以自由基聚合法合成的P(NP29-co-NVF);(b)P(NP29-co-NVF)以1 N HCl(aq)進行80 C水解12小時後的產物P(NP29-co-VAm)之FTIR圖 82
圖4-32 P(NP14-co-NVF)以1 N HCl(aq)進行80 C水解12小時後的產物P(NP14-co-VAm)之NMR圖(水解率=96.1 %) 82
圖4-33 P(NP19-co-NVF)以1 N NaOH(aq)進行80 C水解12小時後的產物P(NP19-co-VAm)之NMR圖(水解率=27.4 %) 83
圖4-34 P(NP19-co-NVF)以1 N HCl(aq)進行80 C水解12小時後的產物P(NP19-co-VAm)之NMR圖(水解率=98.0 %) 83
圖4-35 P(NP29-co-NVF)以1 N HCl(aq)進行80 C水解12小時後的產物P(NP29-co-VAm)之NMR圖(水解率=98.4 %) 84
圖4-36 PNP與不同P(NP-co-VAm)共聚物在pH7.4下穿透率(λ= 450 nm)對溫度的關係圖(a)及溫度一次微分圖(b),溶液濃度為0.1 % (w/v) 86
圖4-37 P(NP19-co-VAm)共聚物在不同pH值下穿透率(λ = 450 nm)對溫度的關係圖(a)及溫度一次微分圖(b) ,溶液濃度為0.1 % (w/v) 87
圖4-38 P(NP14-co-VAm)在 pH7.4、37 C下之粒徑分佈圖 89
圖4-39 (NP19-co-VAm)在 pH7.4、37 C下之粒徑分佈圖 90
圖4-40 P(NP29-co-VAm)在 pH7.4、37 C下之粒徑分佈圖 91
圖4-41不同組成之P(NP-co-VAm)的熱重損失圖 93
圖4-42不同組成之P(NP-co-VAm)的熱重損失圖 93
圖4-43不同P(NP-co-VAm)比例之共聚物的DSC二次升溫曲線圖 94
圖4-44為以自由基聚合法合成的P(NP19-co-NVF) (a)與添加不同NMA含量的PFA3 (b)、PFA5 (c)和PFA10 (d)之FTIR圖 97
圖4-45以自由基聚合法合成的PFA3之NMR圖,起始劑為AIBN,反應溫度60 C,反應時間24小時 98
圖4-46進料比NP:NVF為19:1以自由基聚合法合成的PFA5之NMR圖,起始劑為AIBN,反應溫度60 C,反應時間24小時 98
圖4-47進料比NP:NVF為19:1以自由基聚合法合成的PFA10之NMR圖,起始劑為AIBN,反應溫度60 C,反應時間24小時 99
圖4-48利用自由基聚合法合成不同PFA共聚物,在pH7.4下的穿透率(λ = 450 nm)對溫度的關係圖(a)及溫度一次微分圖(b) ,溶液濃度為0.1 % (w/v) 101
圖4-49利用自由基聚合法合成不同PFA共聚物,在pH5.5下的穿透率(λ = 450 nm)對溫度的關係圖(a)及溫度一次微分圖(b) ,溶液濃度為0.1 % (w/v) 102
圖4-50熱交聯反應式 103
圖4-51 CS (a)以自由基聚合法合成的PFA10 (b)以及CS2/PVA10水凝膠(c)之FTIR圖 104
圖4-52不同組成的CS/PVA水凝膠之凝膠分率(GF) 107
圖4-53不同組成的CS/PVA水凝膠在去離子水(pH 6.8)中的平衡膨潤率 107
圖4-54不同組成的CS/PVA水凝膠在不同溫度及不同pH值緩衝液中的平衡膨潤率 109
圖4-55不同組成的CS/PVA水凝膠在不同溫度及不同pH值緩衝液中的平衡膨潤率 109
圖4-56 不同組成之CS2/PVA之水凝膠的熱重損失圖 112
圖4-57不同組成之CS2/PVA之水凝膠的熱重損失圖 112
圖4-58不同NMA比例之水凝膠的DSC二次升溫曲線圖 113
圖4-59 CS1/PVA3水凝膠之掃描式電子顯微鏡圖(浸泡於蒸餾水中) 115
圖4-60 CS1/PVA5水凝膠之掃描式電子顯微鏡圖(浸泡於蒸餾水中) 116
圖4-61 CS1/PVA10水凝膠之掃描式電子顯微鏡圖(浸泡於蒸餾水中) 117
圖4-62 CS2/PVA3水凝膠之掃描式電子顯微鏡圖(浸泡於蒸餾水中) 118
圖4-63 CS2/PVA5水凝膠之掃描式電子顯微鏡圖(浸泡於蒸餾水中) 119
圖4-64 CS2/PVA10水凝膠之掃描式電子顯微鏡圖(浸泡於蒸餾水中) 120
圖4-65 CS之掃描式電子顯微鏡圖(浸泡於pH5.5 PBS Buffer中) 121
圖4-66 CS1/PVA3水凝膠之掃描式電子顯微鏡圖(浸泡於pH5.5 PBS Buffer中) 122
圖4-67 CS1/PVA5水凝膠之掃描式電子顯微鏡圖(浸泡於pH5.5 PBS Buffer中) 123
圖4-68 CS1/PVA10水凝膠之掃描式電子顯微鏡圖(浸泡於pH5.5 PBS Buffer中) 124
圖4-69 CS2/PVA3水凝膠之掃描式電子顯微鏡圖(浸泡於pH5.5 PBS Buffer中) 125
圖4-70 CS2/PVA5水凝膠之掃描式電子顯微鏡圖(浸泡於pH5.5 PBS Buffer中) 126
圖4-71 CS2/PVA10水凝膠之掃描式電子顯微鏡圖(浸泡於pH5.5 PBS Buffer中) 127
圖4-72 CS之掃描式電子顯微鏡圖(浸泡於pH7.4 PBS Buffer中) 128
圖4-73 CS1/PVA5水凝膠之掃描式電子顯微鏡圖(浸泡於pH7.4 PBS Buffer中) 129
圖4-74 CS1/PVA10水凝膠之掃描式電子顯微鏡圖(浸泡於pH7.4 PBS Buffer中) 130
圖4-75 CS2/PVA3水凝膠之掃描式電子顯微鏡圖(浸泡於pH7.4 PBS Buffer中) 131
圖4-76 CS2/PVA5水凝膠之掃描式電子顯微鏡圖(浸泡於pH7.4 PBS Buffer中) 132
圖4-77 CS2/PVA10水凝膠之掃描式電子顯微鏡圖(浸泡於pH7.4 PBS Buffer中) 133

表目錄
表2-1幾丁聚醣的黏度常數a和K與溶劑、溫度、去乙醯度之關係 11
表2-2 常見LCST型溫度敏感性高分子及其臨界溶液溫度44 15
表2-3 Peppas釋放速率方程式中不同幾何形狀之釋放指數74 28
表3-1自由基聚合合成P(NP-co-NVF)之進料配方 44
表3-2自由基聚合合成P(NP-co-NVF-co-NMA)之進料莫爾比 46
表3-3 CS/PFA之進料比例 48
表4-1不同方法所測定之幾丁聚醣去乙醯度統整表 58
表4-2不同濃度的幾丁聚醣樣品所測得之滯留時間與其黏度參數 59
表4-3 PNVF在12 mL 1 N NaOH(aq) 水解成PVAm的結果整理 66
表4-4 PNVF在12 mL 1 N HCl(aq) 水解成PVAm的結果整理 66
表4-5 不同比例P(NP-co-NVF)之官能基紅外線吸收峰位置整理 73
表4-6不同組成之P(NP-co-NVF)之起始重量損失溫度 (Td, 5%)、最大速率裂解溫度 (Tmax)以及碳焦殘餘量 (C.Y.) 77
表4-7不同P(NP-co-VAm)於pH7.4、37 C下的粒徑尺寸 88
表4-8不同組成之P(NP-co-VAm)之起始重量損失溫度 (Td, 5%)、最大速率裂解溫度 (Tmax)以及碳焦殘餘量 (C.Y.) 92
表4-9進料比NP:NVF為19:1以自由基聚合法合成不同NMA含量的PFA之官能基紅外線吸收峰位置整理 97
表4-10 不同組成之水凝膠經熱交聯及水解後之CS/PVA比例、PVA之凝膠比率(GFPFA)與平衡膨潤率(ESR) 106
表4-11不同組成的CS/PVA水凝膠在不同溫度及pH 5.5緩衝液中的平衡膨潤率 (ESR, %) 108
表4-12不同組成的CS/PVA水凝膠在不同溫度及pH 7.4緩衝液中的平衡膨潤率 (ESR, %) 108
表4-13不同組成的水凝膠在不同溫度下(25與37 oC)之平衡膨潤率差異百分比 (SRD,%) 110
表4-14不同組成的水凝膠在不同溫度下 (25與45 oC)之平衡膨潤率差異百分比 (SRD,%) 110
表4-15不同組成之CS2/PVA水凝膠之起始重量損失溫度 (Td, 5%)、最大速率裂解溫度 (Tmax)以及碳焦殘餘量 (C.Y.) 111

參考文獻 1 張靜宜. 聚癸二酸酐-聚乳酸三團聯共聚物之合成、鑑定及其應用於藥物釋放之研究. 碩士論文 國立清華大學化學工程學系 (2005).
2 黃培傑. 具酸鹼敏感性可快速釋放藥物之載體系統. 碩士論文 國立清華大學化學工程學系, 1-44 (2010).
3 Hao, L., Zhou, Q. & Piao, Y. Albumin-binding prodrugs via reversible iminoboronate forming nanoparticles for cancer drug delivery. Journal of Controlled Release (2020).
4 Xi, L., Li, C. & Wang, Y. Novel thermosensitive polymer-modified liposomes as nano-carrier of hydrophobic antitumor drugs. Journal of Pharmaceutical Sciences (2020).
5 Basha, S. K., Dhandayuthabani, R., Muzammil, M. S. & Kumari, V. S. Solid lipid nanoparticles for oral drug delivery. Materials Today: Proceedings (2020).
6 García-Millán, E., Quintáns-Carballo, M. & Otero-Espinar, F. J. Improved release of triamcinolone acetonide from medicated soft contact lenses loaded with drug nanosuspensions. International journal of pharmaceutics 525, 226-236 (2017).
7 Dhavale, R. P., Dhavale, R., Sahoo, S. & Kollu, P. Chitosan coated magnetic nanoparticles as carriers of anticancer drug Telmisartan: pH-responsive controlled drug release and cytotoxicity studies. Journal of Physics and Chemistry of Solids 148, 109749 (2021).
8 廖景鋒. 可撓式快速溶解微針貼片應用於 DNA 疫苗經皮輸送和增強穩定性. 中山大學理學院暨工學院醫學科技研究所學位論文, 1-97 (2016).
9 Yang, L., Liu, T., Fan, X., Wang, F. & Zheng, L. Advances in poly (N-isopropylacrylamide) based platforms for cell culture. Chinese Journal of Biotechnology 31, 172-182 (2015).
10 Kuo, C.-Y., Don, T.-M., Lin, Y.-T., Hsu, S.-C. & Chiu, W.-Y. Synthesis of pH-sensitive sulfonamide-based hydrogels with controllable crosslinking density by post thermo-curing. Journal of Polymer Research 26, 18 (2019).
11 Muzzarelli, R. A. & Pariser, E. R. Proceedings of the first international conference on chitin/chitosan. (1978).
12 Rudall, K. The chitin/protein complexes of insect cuticles. Advances in insect physiology 1, 257-313 (1963).
13 Muzzarelli, R. A. Chitin. 48-49 (Elsevier, 2013).
14 Sannan, T., Kurita, K. & Iwakura, Y. Studies on chitin, 2. Effect of deacetylation on solubility. Die Makromolekulare Chemie: Macromolecular Chemistry and Physics 177, 3589-3600 (1976).
15 Sashiwa, H. & Shigemasa, Y. Chemical modification of chitin and chitosan 2: preparation and water soluble property of N-acylated or N-alkylated partially deacetylated chitins. Carbohydrate Polymers 39, 127-138 (1999).
16 Zakaria, M. B., Muda, M. W. & Abdullah, M. P. Chitin and chitosan: the versatile environmentally friendly modern materials. Collection of working papers 28 Penerbit University (1995).
17 Shariatinia, Z. & Nikfar, Z. Synthesis and antibacterial activities of novel nanocomposite films of chitosan/phosphoramide/Fe3O4 NPs. International journal of biological macromolecules 60, 226-234 (2013).
18 Shariatinia, Z., Nikfar, Z., Gholivand, K. & Abolghasemi Tarei, S. Antibacterial activities of novel nanocomposite biofilms of chitosan/phosphoramide/Ag NPs. Polymer Composites 36, 454-466 (2015).
19 Leuba, J. & Stossel, P. in Chitin in nature and technology 215-222 (Springer, 1986).
20 Younes, I. & Rinaudo, M. Chitin and chitosan preparation from marine sources. Structure, properties and applications. Marine drugs 13, 1133-1174 (2015).
21 Chen, C.-S., Liau, W.-Y. & Tsai, G.-J. Antibacterial effects of N-sulfonated and N-sulfobenzoyl chitosan and application to oyster preservation. Journal of Food Protection 61, 1124-1128 (1998).
22 Chuang, C.-Y., Don, T.-M. & Chiu, W.-Y. Preparation of environmental-responsive chitosan-based nanoparticles by self-assembly method. Carbohydrate polymers 84, 765-769 (2011).
23 Tôei, K. & Kohara, T. A conductometric method for colloid titrations. Analytica Chimica Acta 83, 59-65 (1976).
24 Terayama, H. Method of colloid titration (a new titration between polymer ions). Journal of Polymer Science 8, 243-253 (1952).
25 Dos Santos, Z., Caroni, A., Pereira, M., Da Silva, D. & Fonseca, J. Determination of deacetylation degree of chitosan: a comparison between conductometric titration and CHN elemental analysis. Carbohydrate Research 344, 2591-2595 (2009).
26 Muzzarelli, R. A. & Rocchetti, R. Determination of the degree of acetylation of chitosans by first derivative ultraviolet spectrophotometry. Carbohydrate Polymers 5, 461-472 (1985).
27 Lavertu, M. et al. A validated 1H NMR method for the determination of the degree of deacetylation of chitosan. Journal of pharmaceutical and biomedical analysis 32, 1149-1158 (2003).
28 Heux, L., Brugnerotto, J., Desbrieres, J., Versali, M.-F. & Rinaudo, M. Solid state NMR for determination of degree of acetylation of chitin and chitosan. Biomacromolecules 1, 746-751 (2000).
29 Graham K. Moore & A.F.Roberts, G. International Journal of Biological Macromolecules V2 (1980).
30 Baxter, A., Dillon, M., Taylor, K. A. & Roberts, G. A. Improved method for ir determination of the degree of N-acetylation of chitosan. International journal of biological macromolecules 14, 166-169 (1992).
31 Duarte, M., Ferreira, M., Marvao, M. & Rocha, J. An optimised method to determine the degree of acetylation of chitin and chitosan by FTIR spectroscopy. International Journal of Biological Macromolecules 31, 1-8 (2002).
32 Wang, W., Bo, S., Li, S. & Qin, W. Determination of the Mark-Houwink equation for chitosans with different degrees of deacetylation. International Journal of Biological Macromolecules 13, 281-285 (1991).
33 Wu, A. C., Bough, W. A., Conrad, E. C. & Alden Jr, K. E. Determination of molecular-weght distribution of chitosan by high-performance liquid chromatography. Journal of Chromatography A 128, 87-99 (1976).
34 Mano, J. F. Stimuli‐responsive polymeric systems for biomedical applications. Advanced Engineering Materials 10, 515-527 (2008).
35 Sá-Lima, H., Caridade, S. G., Mano, J. F. & Reis, R. L. Stimuli-responsive chitosan-starch injectable hydrogels combined with encapsulated adipose-derived stromal cells for articular cartilage regeneration. Soft Matter 6, 5184-5195 (2010).
36 Marques, N. d. N., Maia, A. M. d. S. & Balaban, R. d. C. Development of dual-sensitive smart polymers by grafting chitosan with poly (N-isopropylacrylamide): an overview. Polímeros 25, 237-246 (2015).
37 Wang, H., Yang, L. & Rempel, G. L. Preparation of p H‐R esponsive Polymer Core–S hell Nanospheres for Delivery of Hydrophobic Antineoplastic Drug Ellipticine. Macromolecular bioscience 14, 166-172 (2014).
38 Tian, E., Wang, J. & Zheng, Y. Colorful humidity sensitive photonic crystal hydrogel. Journal of Materials Chemistry 18, 1116-1122 (2008).
39 Yan, N., Zhang, J. & Yuan, Y. Thermoresponsive polymers based on poly-vinylpyrrolidone: applications in nanoparticle catalysis. Chemical Communications 46, 1631-1633 (2010).
40 Valmikinathan, C. M., Chang, W., Xu, J. & Yu, X. Self assembled temperature responsive surfaces for generation of cell patches for bone tissue engineering. Biofabrication 4, 035006 (2012).
41 Zhang, C., Yan, L. & Wang, X. Progress, challenges, and future of nanomedicine. Nano Today 35, 101008 (2020).
42 Schmaljohann, D. Thermo- and pH-responsive polymers in drug delivery. Advanced drug delivery reviews 58, 1655-1670 (2006).
43 Gandhi, A., Paul, A., Sen, S. O. & Sen, K. K. Studies on thermoresponsive polymers: Phase behaviour, drug delivery and biomedical applications. asian journal of pharmaceutical sciences 10, 99-107 (2015).
44 Roy, D., Brooks, W. L. & Sumerlin, B. S. New directions in thermoresponsive polymers. Chemical Society Reviews 42, 7214-7243 (2013).
45 Constantin, M., Cristea, M., Ascenzi, P. & Fundueanu, G. Lower critical solution temperature versus volume phase transition temperature in thermoresponsive drug delivery systems. Express Polym Lett 5, 839-848 (2011).
46 Pei, Y., Chen, J. & Yang, L. The effect of pH on the LCST of poly (N-isopropylacrylamide) and poly (N-isopropylacrylamide-co-acrylic acid). Journal of Biomaterials Science, Polymer Edition 15, 585-594 (2004).
47 Otake, K., Inomata, H., Konno, M. & Saito, S. Thermal analysis of the volume phase transition with N-isopropylacrylamide gels. Macromolecules 23, 283-289 (1990).
48 Cole, M. A., Voelcker, N. H., Thissen, H. & Griesser, H. J. Stimuli-responsive interfaces and systems for the control of protein–surface and cell–surface interactions. Biomaterials 30, 1827-1850 (2009).
49 Purushotham, S., Chang, P., Rumpel, H. & Kee, I. Thermoresponsive core–shell magnetic nanoparticles for combined modalities of cancer therapy. Nanotechnology 20, 305101 (2009).
50 Chuang, C. Y., Don, T. M. & Chiu, W. Y. Synthesis and properties of chitosan‐based thermo‐and pH‐responsive nanoparticles and application in drug release. Journal of Polymer Science Part A: Polymer Chemistry 47, 2798-2810 (2009).
51 Gao, W., Chan, J. M. & Farokhzad, O. C. pH-responsive nanoparticles for drug delivery. Molecular pharmaceutics 7, 1913-1920 (2010).
52 Manne, A. A., Arigela, B. & Giduturi, A. K. Pterocarpus marsupium Roxburgh heartwood extract/chitosan nanoparticles loaded hydrogel as an innovative wound healing agent in the diabetic rat model. Materials Today Communications 26, 101916.
53 Philippova, O. E., Hourdet, D., Audebert, R. & Khokhlov, A. R. pH-responsive gels of hydrophobically modified poly (acrylic acid). Macromolecules 30, 8278-8285 (1997).
54 Pelton, R. Polyvinylamine: A tool for engineering interfaces. Langmuir 30, 15373-15382 (2014).
55 Kröner, M., Dupuis, J. & Winter, M. N‐Vinylformamide—Syntheses and Chemistry of a Multifunctional Monomer. Journal für praktische Chemie 342, 115-131 (2000).
56 Gu, L., Zhu, S. & Hrymak, A. Acidic and basic hydrolysis of poly (N‐vinylformamide). Journal of applied polymer science 86, 3412-3419 (2002).
57 Chen, Q., Xu, K., Zhang, W., Song, C. & Wang, P. Preparation and characterization of poly (N-isopropylacrylamide)/polyvinylamine core-shell microgels. Colloid and Polymer Science 287, 1339 (2009).
58 Ilavský, M. Effect of electrostatic interactions on phase transition in the swollen polymeric network. Polymer 22, 1687-1691 (1981).
59 Zhang, X.-Z., Yang, Y.-Y., Wang, F.-J. & Chung, T.-S. Thermosensitive poly (n-isopropylacrylamide-co-acrylic acid) hydrogels with expanded network structures and improved oscillating swelling− deswelling properties. Langmuir 18, 2013-2018 (2002).
60 Liu, F. & Urban, M. W. Recent advances and challenges in designing stimuli-responsive polymers. Progress in polymer science 35, 3-23 (2010).
61 Wang, L., Shelton, R. & Cooper, P. Evaluation of sodium alginate for bone marrow cell tissue engineering. Biomaterials 24, 3475-3481 (2003).
62 Knill, C., Kennedy, J. & Mistry, J. Alginate fibres modified with unhydrolysed and hydrolysed chitosans for wound dressings. Carbohydrate Polymers 55, 65-76 (2004).
63 Hoare, T. R. & Kohane, D. S. Hydrogels in drug delivery: Progress and challenges. Polymer 49, 1993-2007 (2008).
64 Mu, R., Liu, B., Chen, X., Wang, N. & Yang, J. Hydrogel adsorbent in industrial wastewater treatment and ecological environment protection. Environmental Technology & Innovation 20, 101107 (2020).
65 Li, T., Zhang, X., Xia, B. & Ma, P. Hybrid double-network hydrogels with excellent mechanical properties. New Journal of Chemistry 44, 16569-16576 (2020).
66 Mondal, S., Das, S. & Nandi, A. K. A review on recent advances in polymer and peptide hydrogels. Soft Matter 16, 1404-1454 (2020).
67 林永信. 磺酸化聚胺酯/幾丁聚醣半互穿型網狀結構體之製備研究. 碩士論文 國立臺灣大學 (2002).
68 Mäder, K., Lehner, E., Liebau, A. & Plontke, S. K. Controlled drug release to the inner ear: concepts, materials, mechanisms, and performance. Hearing Research 368, 49-66 (2018).
69 Bajpai, A. K., Shukla, S. K., Bhanu, S. & Kankane, S. Responsive polymers in controlled drug delivery. Progress in Polymer Science 33, 1088-1118 (2008).
70 Zarzycki, R., Modrzejewska, Z. & Nawrotek, K. Drug release from hydrogel matrices. Ecol Chem Eng S 17, 117-136 (2010).
71 Siepmann, J. & Siepmann, F. Modeling of diffusion controlled drug delivery. Journal of controlled release 161, 351-362 (2012).
72 Ritger, P. L. & Peppas, N. A. A simple equation for description of solute release II. Fickian and anomalous release from swellable devices. Journal of controlled release 5, 37-42 (1987).
73 Ritger, P. L. & Peppas, N. A. A simple equation for description of solute release I. Fickian and non-fickian release from non-swellable devices in the form of slabs, spheres, cylinders or discs. Journal of controlled release 5, 23-36 (1987).
74 Siepmann, F., Siepmann, J., Walther, M., MacRae, R. & Bodmeier, R. Polymer blends for controlled release coatings. Journal of Controlled Release 125, 1-15 (2008).
75 Bajpai, A. & Rajpoot, M. Release and diffusion of sulfamethoxazole through acrylamide‐based hydrogel. Journal of applied polymer science 81, 1238-1247 (2001).
76 Bajpai, A. & Bhanu, S. Immobilization of α-amylase in vinyl-polymer-based interpenetrating polymer networks. Colloid and Polymer Science 282, 76-83 (2003).
77 Lin, C.-C. & Metters, A. T. Hydrogels in controlled release formulations: network design and mathematical modeling. Advanced drug delivery reviews 58, 1379-1408 (2006).
78 岑翰儒. 幾丁聚醣接枝聚氮-異丙基丙烯醯胺薄膜的合成及其性質研究. 碩士論文 淡江大學 (2004).
79 余虹德. 幾丁聚醣/磷酸三鈣複合薄膜的製備與性質. 碩士論文 (2006).
80 Tripathy, J., Mishra, D. K. & Behari, K. Graft copolymerization of N-vinylformamide onto sodium carboxymethylcellulose and study of its swelling, metal ion sorption and flocculation behaviour. Carbohydrate Polymers 75, 604-611 (2009).
81 Qiu, Y., Zhang, T., Ruegsegger, M. & Marchant, R. E. Novel nonionic oligosaccharide surfactant polymers derived from poly (vinylamine) with pendant dextran and hexanoyl groups. Macromolecules 31, 165-171 (1998).
82 Witek, E., Pazdro, M. & Bortel, E. Mechanism for base hydrolysis of poly (N‐vinylformamide). Journal of Macromolecular Science, Part A 44, 503-507 (2007).
83 Gu, L., Zhu, S., Hrymak, A. N. & Pelton, R. H. The Nature of Crosslinking in N‐Vinylformamide Free‐Radical Polymerization. Macromolecular rapid communications 22, 212-214 (2001).
84 Evanghelidis, A., Beregoi, M. & Diculescu, V. C. Flexible Delivery Patch Systems based on Thermoresponsive Hydrogels and Submicronic Fiber Heaters. Scientific Reports 8, 1-10 (2018).
85 Bucatariu, S., Fundueanu, G. & Prisacaru, I. Synthesis and characterization of thermosensitive poly (N-isopropylacrylamide-co-hydroxyethylacrylamide) microgels as potential carriers for drug delivery. Journal of Polymer Research 21, 580 (2014).
86 Shah, L. A., Farooqi, Z. H., Naeem, H., Shah, S. M. & Siddiq, M. Synthesis and characterization of poly (N-isopropylacrylamide) hybrid microgels with different cross-linker contents. Journal of the Chemical Society of Pakistan 35, 1522-1529 (2013).
87 Yang, H.-W., Lee, A.-W., Huang, C.-H. & Chen, J.-K. Characterization of poly (N-isopropylacrylamide)–nucleobase supramolecular complexes featuring bio-multiple hydrogen bonds. Soft Matter 10, 8330-8340 (2014).
88 Yamamoto, K., Imamura, Y. & Nagatomo, E. Synthesis and functionalities of poly (N‐vinylalkylamide). XIV. Polyvinylamine produced by hydrolysis of poly (N‐vinylformamide) and its functionalization. Journal of applied polymer science 89, 1277-1283 (2003).
89 Saeed, A., Georget, D. M. & Mayes, A. G. Synthesis, characterisation and solution thermal behaviour of a family of poly (N-isopropyl acrylamide-co-N-hydroxymethyl acrylamide) copolymers. Reactive and Functional Polymers 70, 230-237 (2010).

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