改質聚乳酸奈米纖維以促進親水性藥物之持續釋放

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姓名

洪佩芝(Pei-Chih Hung) 查詢紙本館藏

畢業系所

化學工程與材料工程學系

論文名稱

改質聚乳酸奈米纖維以促進親水性藥物之持續釋放
(Modification of Electrospun Polylactic Acid Nanofibers to Sustain Hydrophilic Drug Delivery)

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摘要(中)

慢性傷口因癒合時間較長，需要開發抗菌敷料來避免感染風險。聚乳酸(PLA)為常見敷料材料，具有可降解性以及生物相容性，然而其疏水性使其不易包覆藥物及持續釋放，因此本研究將介孔二氧化矽奈米粒子(MSN)混入PLA進行電紡絲，以用於裝載抗生素去氧羥四環素(DCH)。透過測試發現MSN的加入不但能夠增加纖維的熱穩定性也能增加機械強度，且纖維具有高透氣性，可以有效保護傷口。經由溶脹率實驗結果了解到MSN結構上的氫氧基能增加親水性，使得溶脹率提高，此特性不但能促進傷口滲出液的吸收，也有助於改善纖維的高疏水性。因此在藥物釋放實驗中，DCH的釋放會隨著MSN在纖維中的比例而提升。其中D-P-M12會造成初始爆發釋放，因此對成纖維細胞造成明顯毒性，但此毒性並未在其他載藥複合纖維發現。最後，在抗菌實驗中證實，雖然D-P-M12的初始爆發釋放使其在紙錠擴散實驗中擁有最大的抗菌抑制區，但其效果會隨時間下降，相較之下，D-P-M10組即使到了第四天都可以維持99%的抗菌效果，因此考量到穩定的抗菌能力及不會影起細胞毒性，D-P-M10纖維極具成為慢性傷口敷料的潛力。

摘要(英)

Considering the long healing time of chronic wounds, it is necessary to develop antibacterial dressings to avoid the risk of infection. Polylactic acid (PLA) is a frequently investigated dressing material due to its biodegradability and biocompatibility. However, its hydrophobicity makes it difficult to load drugs for sustained release. Therefore, in this study, mesoporous silica nanoparticles (MSN) were mixed with PLA to electrospin composite nanofibers for loading doxycycline hyclate (DCH), an antibiotic. These fibers owned high permeability. In addition, the added MSN not only increased thermal stability but also reinforced composite nanofibers, suggesting that composite fibers were suitable to physically protect wounds. The hydroxyl groups on MSNs increased the hydrophilicity to enhance the swelling rates of composite fibers, which not only promoted the absorption of wound exudate but also improved wettability of the composite nanofiber. Therefore, the release experiments showed that DCH delivery increased with the ratio of MSN in the composite nanofibers. Among them, D-P-M12 demonstrated an initial burst release, which thus significantly reduced proliferation rates of fibroblasts. However, other composite fibers did not occur this difficulty. Regrading antibacterial effects, D-P-M12 owned the largest inhibition zone in disc-diffusion experiments due to its initial burst release, but its antibacterial efficiency decreased over time. In contrast, the D-P-M10 group maintained 99% of antibacterial effects for 4 days. Therefore, D-P-M10 fibers were potential dressings for chronic wounds due to its stable antibacterial ability without causing cytotoxicity.

關鍵字(中)

★ 聚乳酸奈米纖維
★ 親水性藥物
★ 持續釋放

關鍵字(英)

★ Poly(lactic acid) nanofibers
★ Hydrophilic drug
★ Sustained release

論文目次

目錄
摘要 I
Abstract II
致謝 III
目錄 IV
圖目錄 VIII
表目錄 XI
第一章緒論 1
1-1 研究背景 1
1-2 研究目的 3
第二章文獻回顧 5
2-1 慢性傷口 5
2-1-1 糖尿病傷口修復 5
2-2 電紡絲 8
2-2-1電紡絲原理 8
2-2-2 電紡絲在傷口敷料之應用 10
2-3 聚乳酸 11
2-3-1 聚乳酸之簡介 11
2-3-2聚乳酸之性質 12
2-3-3 聚乳酸在傷口敷料之應用 13
2-4藥物輸送 15
2-4-1藥物釋放從載藥電紡絲釋放的動力學 16
2-4-2 改善疏水性材料的釋放特性 18
2-5 介孔二氧化矽奈米粒子 22
2-5-1 介孔二氧化矽奈米粒子之簡介 22
2-5-2 介孔二氧化矽奈米粒子之合成 22
2-5-3介孔二氧化矽奈米粒子之應用 24
2-6去氧羥四環素 26
2-6-1 去氧羥四環素之簡介 26
2-6-2 去氧羥四環素之特性 27
2-6-3 去氧羥四環素在慢性傷口之應用 28
第三章材料與方法 30
3-1 實驗材料 30
3-2 實驗儀器 32
3-3 實驗方法 34
3-3-1 介孔二氧化矽奈米粒子合成 34
3-3-2 電紡絲溶液製備 35
3-3-3 電紡絲纖維製備 38
3-3-4 SEM之樣本製備 39
3-3-5 TEM之樣本製備 41
3-3-6 SAXS/TGA/DSC之樣本製備 41
3-3-7 FTIR樣本製備 41
3-3-8 萬能拉伸試驗機樣本製備 41
3-3-9 電紡絲纖維溶脹率(Swelling ratio) 43
3-3-10 電紡絲纖維水蒸氣穿透率(Water Vapor Transmission rate, WVTR) 43
3-3-11 藥物釋放實驗 44
3-3-12 抗菌實驗 45
3-3-13 NIH 3T3細胞培養 48
3-3-14 細胞存活率實驗(MTT assay) 53
第四章結果與討論 55
4-1 介孔二氧化矽奈米粒子合成之鑑定 55
4-1-1 介孔二氧化矽奈米粒子形態及結構鑑定 55
4-2 聚乳酸/介孔二氧化矽/去氧羥四環素之複合奈米電紡絲性質 58
4-2-1複合電紡絲形態與直徑分布 58
4-2-2複合電紡絲之SAXS分析 61
4-2-3複合電紡絲之熱分析 62
4-2-4複合電紡絲之FTIR分析 64
4-2-5複合電紡絲之機械性質分析 66
4-2-6 複合纖維之溶脹率 68
4-2-7 複合纖維之水蒸氣穿透率(WVTR) 70
4-3複合電紡絲之藥物釋放曲線 71
4-4 複合電紡絲對細胞之影響 73
4-4-1 細胞培養於複合纖維上之SEM圖 73
4-4-2 細胞培養於複合纖維上之增生率 75
4-5電紡絲之抗菌活性 77
4-5-1固態培養之抗菌活性 77
4-5-2 液態培養之抑菌率 79
第五章結論 81
第六章參考資料 84

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指導教授

胡威文(Wei-Wen Hu)

審核日期

2021-10-28

推文