製備溫感性抗菌水凝膠以應用在創傷敷材

Fabrication of thermo-responsive antibacterial hydrogels for wound dressing

邱詠翰(Yung-Han Chiu)

指導教授 ： 董崇民

淡江大學/工學院/化學工程與材料工程學系碩士班/碩士(2020年)

https://doi.org/10.6846/TKU.2020.00929

摘要

本研究為利用紫外光起始自由基聚合法合成具溫度敏感性的抗菌水凝膠，以氮-異丙基丙烯醯胺 (N-isopropylacrylamide，NIPAAm，NP)為主體，添加親水性良好的2-丙烯醯胺-2-甲基丙磺酸 (2-acrylamido-2-methylpropane sulfonic acid，AMPS)、2-丙烯酸羥乙酯 (2-Hydroxyethyl acrylate，HEA)以及幾丁聚醣 (Chitosan，CS)，並加入N,N'-亞甲基雙丙烯醯胺 (N,N'-methylenebisacrylamide，MBA)和2,2-二乙氧基苯乙酮 (2,2-diethoxyacetophenone，DEAP)做為交聯劑與光起始劑，形成半互穿型的網狀水凝膠，利用FTIR對其化學結構進行分析，確定水凝膠有成功合成，並用SEM觀察水凝膠之表面型態，接著進行拉伸機械性質、熱性質、膨潤測試、藥物包覆/釋放、生物相容性、抗菌等一系列測試，對水凝膠進行評估，根據拉伸測試結果可以知道交聯劑及NP含量的提升都可以增加抗張強度及破壞伸長率，膨潤的情況下，抗張強度與拉伸率最高可以達到67.5 kPa和55.6%；熱性質方面，隨著NP相對含量的提升，玻璃轉移溫度可以從N9A1-1.0的116 oC提升至N99A1-1.0的125 oC，有助於增強水凝膠的熱穩定性；膨潤率的結果顯示出水凝膠的平衡膨潤率隨著交聯劑和NP的相對含量提升而下降；水凝膠對於鹽酸四環素 (Tetracycline hydrochloride，TC)的包覆與釋放結果可以發現，其鹽酸四環素的包覆率會隨著NP的含量提高而下降，藥物釋放行為不會受到pH值所影響且經由動力學的描述皆屬於異常擴散 (Anomalous transport，n介於0.5到1.0之間)；透過人類表皮纖維母細胞HS 68所進行的生物相容性結果可以知道水凝膠對於細胞是沒有毒性的；大腸桿菌的抗菌實驗顯示出水凝膠具有抗菌性。

關鍵字

創傷敷材 ； 水凝膠 ； 溫感性 ； 氮-異丙基丙烯醯胺 ； 幾丁聚醣

並列摘要

In this study, N-isopropylacrylamide, 2-acrylamido-2-methylpropane sulfonic acid and 2-Hydroxyethyl acrylate were polymerized by UV-initiated free radical polymerization in the presence of chitosan to prepare the semi-interpenetrating hydrogels with thermo-responsive and antibacterial properties. N,N'-methylenebisacrylamide and 2,2-diethoxyacetophenone were applied as crosslinker and photo-initator, respectively. Chemical structure and surface morphology of hydrogels were characterized by respective FTIR and SEM. Furthermore, a series of tests iucluding tensile mechanical properties, thermal properties, swelling, drug loading/release, biocompatibility, antibacterial properties were carried out to evaluate the prepared hydrogels. The results showed that increasing the contents of NP and crosslinking agent would enhance the tensile mechanical properties in which the tensile strength and enlongation at break could reach 67.5 kPa and 55.6%, respectively, under swelling state. Moreover, glass transition temperature (Tg) increased from 116 oC for the N9A1-1.0 to 125 oC at the NP content was increased. The results also showed that the increases of crosslinker and NP content would reduce the equilibrium swelling ratio. The loading amount of tetracycline hydrochloride in the hydrogels decreased with the increasing NP content and the drug-release behavior would not be influenced by pH value. The drug-release behavior could be described by an empirical equation of non-fickian diffusion. In vitro studies showed that hydrogels were non-toxic and they could promote cell growth of human foreskin fibroblast (HS-68). The antibacterial test against E. coli showed that these hydrogels had antibacterial properties.

並列關鍵字

Wound dressing ； Hydrogel ； Thermosensitive ； N-isopropylacrylamide ； Chitosan

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