本論文以果膠(pectin)為主要材料，氯化鈣為交聯劑(crosslinker)混摻聚乙烯醇(PVA)或海藻酸鈉(Alg)來製備水膠薄膜，並探討其藥物釋放行為及生物相容性。本論文共分為三大部分: 第一部份為酸鹼與溫度敏感型pectin/PVA混摻水膠之載入釋放行為及血液相容性探討。第二部份為酸鹼敏感型pectin/Alg混摻水膠在模擬腸胃液之藥物控制釋放行為探討。第三部份為改質pectin/Alg/PVA混摻水膠之血液相容性、生物相容性與表面行為探討。
第一部份之pectin/PVA混摻水膠薄膜，在pH 2~12 進行酸鹼敏感測試，然後在2~45 °C之下測量混合焓(Hmix)。其含水量(water content)可用DSC檢測。Ca2+交聯劑的影響可利用彈性模數、有效交聯密度(effective crosslinking density, νe)及高分子－溶劑之交互作用參數(χ)由Flory theory 計算。Pectin/PVA混摻水膠薄膜經由茜素紅載入實驗的結果符合Langmuir等溫吸附方程式，而其釋放動力學則是較符合Fickian diffusion模式。血液相容性測試結果顯示pectin/PVA混摻水膠薄膜的蛋白質及血小板之吸附隨果膠含量增加而減少。
第二部份的pectin/Alg混摻水膠薄膜作為氨比西林(ampicillin)的控制釋放載體，並比較不同混摻比水膠在模擬腸胃液中控制釋放特性上的差異。此混摻水膠薄膜對氨比西林的載藥量符合Langmuir吸附等溫線，其氨比西林藥物在模擬胃液(simulated gastric fluid, pH 1.2)、模擬結腸液(simulated colonic fluid, pH 6.8)及模擬小腸液(simulated intestinal fluid, pH 7.4)的釋放動力學遵循Fickian diffusion機制。Pectin/Alg混摻水膠薄膜釋放氨比西林速率與其Ca2+交聯度、果膠含量、果膠酶及pH值有相關性。實驗結果證明pectin/Alg混摻水膠可適用於腸道的藥物區域傳遞系統(localized delivery of drug)。
第三部份以pectin/Alg/PVA混摻水膠為基材，利用氧電漿活化表面，接枝丙烯酸(acrylic acid)於膜表面產生-COOH基團，與幾丁聚醣(chitosan)結合，再以幾丁聚醣上的NH2與肝素(heparin)或透明質酸(hyaluronic acid)共價結合，分別探討其表面改質後水膠的親水性、血液相容性、抑菌性、與L929纖維母細胞毒性，並且分析血液凝固性。改質後pectin/Alg/PVA混摻薄膜的表面性質可利用XPS和染料分析出表面接枝結構。表面接枝肝素和透明質酸可增加薄膜之親水性。表面經接枝幾丁聚醣後對大腸桿菌(Escherichia coli)及金黃色葡萄球菌(Staphylococcus aureus)有抑菌性。蛋白質吸附試驗發現未改質的pectin/Alg/PVA混摻薄膜其人體血清白蛋白(HSA)或人體血漿纖維蛋白原(HPF)之吸附量較接枝肝素的pectin/Alg/PVA-CS-HEP水膠和接枝透明質酸的pectin/Alg/PVA-CS-HA水膠後而有負電荷表面者為高。活化部分凝血酶原時間(APPT)的結果發現接枝肝素之pectin/Alg /PVA-CS-HEP水膠的凝血時間有大幅增長且血小板吸附降低。此外經改質前後的水膠薄膜以L929纖維母細胞觀察其生物毒性，其結果顯示改質後pectin/Alg/PVA混摻水膠未析出有毒物質。
總結實驗結果顯示改質後果膠的混摻薄膜可應用在藥物制放系統及生物相容性包括血液相容性，細胞相容性及抑菌性。本論文的改質方式可使果膠混摻薄膜在生醫材料的領域上有極大的潛力。

In this study, pectin was blended with polyvinyl alcohol (PVA) or sodium alginate (Alg) and crosslinked with calcium ions into blend hydrogel membranes. The presented work was divided into three parts to study. Part I investigated the controlled release behavior and hemocompatibility of pH- and thermo-sensitivity pectin/PVA blend hydrogels. Part II was focused on the evaluation of the drug release mechanism of pH-sensitive pectin/Alg blend hydrogels in simulated physiological fluids. Part III immobilized the chitosan/hyaluronic acid/heparin multilayer on pectin/PVA /Alg blend membranes and the effect on the biocompatibility of pectin/ Alg/PVA blend membranes.
In the first part, the pH- and temperature-dependent swelling behavior of pectin/PVA blend hydrogels was examined under pH from 2 to 12 and at temperatures from 2 to 45 °C and the enthalpy of mixing (Hmix) was investigated. The water structure in the hydrogels was measured by differential scanning calorimetry (DSC). The influence of Ca2+ content on the network structure of pectin/PVA blend hydrogels was investigated in terms of compressive elastic modulus, effective crosslinking density (νe) and the polymer–solvent interaction parameter (χ) based on the Flory theory. The loading of alizarin red S (ARS) followed the Langmuir isotherm mechanism and the release kinetics of the pectin/PVA blend hydrogels at 37 °C followed Fickian diffusion. The amount of protein adsorbed and platelets adhered on the pectin/PVA blend hydrogels were significantly curtailed with increasing pectin content, thereby showing improved blood compatibility. The pectin/PVA blend hydrogels were proven to be non- cytotoxic evaluated in vitro by L-929 fibroblast incubation.
In the second part, pectin/Alg blend hydrogels was loaded with ampicillin to evaluate the release mechanism in simulated physiological fluids. The loading capacity of ampicillin followed the Langmuir isotherm model. The drug release of pectin/Alg blend hydrogels were performed in simulated gastric fluid (SGF, pH 1.2), simulated colonic fluid (SCF, pH 6.8) and simulated intestinal fluid (SIF, pH 7.4). The pectin/Alg blend hydrogels with higher pectin content exhibited higher drug release rate. The release rate of ampicillin in SIF was higher than that in SCF and SGF and followed a Fickian diffusion mechanism. The results showed that the release kinetics was significantly dependent on the crosslinking degree of the pectin/Alg blend hydrogels and the physiological pH. The results indicated that pectin/Alg blend hydrogels may be useful for the localized delivery of drug in the intestinal environment.
In the last part, aiming to improve the hydrophilicity, antibacterial activity, cytocompatibility and hemocompatibility of pectin/Alg/PVA blend hydrogels, pectin/Alg/PVA blend films were treated with oxygen plasma, grafted with chitosan (CS), and followed by covalent-immobilization of either heparin (HEP) or hyaluronic acid (HA). The surface graft density of modified pectin/Alg/PVA films was detected by X-ray photoelectron spectroscopy (XPS) and dyeing. After immobilizing chitosan, pectin/PVA /Alg-CS blend films acquired antibacterial activity against Escherichia coli and Staphylococcus aureus. The adsorption of human serum albumin (HSA) and human plasma fibrinogen (HPF) on pectin/Alg/PVA-CS-HEP and pectin/Alg/PVA-CS-HA films was lower comparing to that of pectin/Alg/PVA. Moreover, HEP immobilization could effectively reduce platelet adhesion and prolong the blood coagulation time, thereby improve the blood compatibility of pectin/Alg/PVA blend films. In addition, the growth of L929 fibroblasts was improved for HEP or HA immobilized pectin/Alg/PVA, suggesting this surface modification was non-cytotoxic. Furthermore, pectin/Alg/PVA-CS-HEP and pectin/Alg/PVA-CS-HA exhibited higher cell proliferation than pectin/Alg/PVA.
Overall result demonstrated that such an easy processing and rapid method should have good potential for modification of pectin/PVA, pectin/Alg and pectin/Alg/PVA blend hydrogels in the application of controlled drug delivery system and biocompatibility, such as cytocompatibility, hemocompatibility and antibacterial activity.

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