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  • 學位論文

光敏感型褐藻酸鹽水凝膠複合材料的合成與其光控藥物釋放性質分析

Synthesis of Photoresponsive Alginate Hybrid Hydrogels and Its Photo-Controlled Drug Release Behavior

指導教授 : 朱智謙

摘要


本篇研究分別成功合成出帶有β-環糊精(β-Cyclodextrins;β-CD)的褐藻酸高分子 (β-CD-Alg),以及兩側尾端帶有偶氮苯衍生物 (Azobenzene derivative;Az)的聚乙烯二醇(Az-PEG);接著將兩者混合後加入Ca2+離子進行交聯而得到黃色的褐藻酸水凝膠複合材料。由於β-CD及反式Az分子可進行主客反應形成內嵌錯合物,順式Az分子則無法與β-CD結合,因此簡單透過光致順反異構化便可以控制主客錯合物的生成與消失。我們所製備出來的Alg水凝膠,除了具有透過Ca2+離子形成的網狀交聯結構外,Alg高分子鏈衍生的β-CD基團與反式Az分子間的主客反應,提供了更多的交聯點,進而提升了水凝膠的機械性質。此外,因為在照射紫外光後Az變成順式結構,而不會與β-CD產生主客反應,進而讓複合型水凝膠結構產生降解,而逐漸釋放出所包覆的染料分子。我們分別由2D Noesy與穿透率實驗證實β-CD與Az-PEG會形成主客反應;由螢光光譜分析儀證明將RhB染料分子包覆至水凝膠內,隨著照射紫外光時間增加,染料分子逐漸從膠內釋放出來,使膠體螢光強度變弱;最後由SEM觀察六組分別由Alg水凝膠、含有Az-PEG的Alg水凝膠、β-CD-Alg水凝膠、含有Az-PEG與β-CD-Alg複合型水凝膠及含有Az-PEG與β-CD-Alg溶液放置二十小時後所製備的複合型水凝膠分別在照射紫外光前後及含有Az-PEG與β-CD-Alg複合型水凝膠照射可見光前後觀察凝膠表面變化,發現具有Az-PEG與β-CD-Alg所製備的複合型水凝膠會經由照射紫外光後,凝膠表面產生許多孔洞。所以經由一連串實驗果證實,藉由光致順反異構化可以控制複合型水凝膠釋放小分子的能力,可被運用在藥物與蛋白質釋放的相關研究上,且在弱酸條件下,釋放效果更好,更可以應用在傷口敷材上。

並列摘要


Alginate(Alg),which is commonly isolated from brown algae,is an anionic linear polysaccharide composed of two saccharides: epimeric β-D-mannuronate (M) and α-L-guluronate (G). The M and G monomers are covalently bonded through 1,4-glycosidic linkages and arranged into either homopolymeric blocks (MM and GG) or alternating blocks (MGMG) along the polymeric backbone. According to the “egg-box” model,two facing GG blocks can be coordinated with divalent Ca2+ ions, resulting in interchain crosslinking and hydrogel formation,especially rich in GG blocks can incorporate more ionic interactions between chains and usually form a gel with high mechanical integrity. We developed a photoresponsive hybrid alginate semi-IPN that contains crosslinked β-Cyclodextrin-grafted alginate (β-CD-Alg) and interpenetrating diazobenzene-terminated poly(ethylene glycol) (Az-PEG),because of the size and shape of the CD cavity,trans-Az and β-CD can form a favorable inclusion complex through host-guest affinity,whereas cis-Az is excluded from the complexation. Therefore,the hybrid gel network features Ca2+ ions as cross-linkers as well as numerous junction points composed of β-CD and trans-Az inclusion complexes. Moreover,UV light irradiation induces efficient trans-to-cis isomerization. Accordingly,the hybrid alginate hydrogel is sensitive to the UV light used to facilitate trans-to-cis photoisomerization,which results in the dissociation of the inclusion complex and partial gel degradation. Thus,a light trigger can accelerate the release rate of small molecules entrapped within the gel. In addition to causing spontaneous drug release during gel swelling, this strategy entails using a bulk alginate hydrogel as a photocontrollable release system. In conclusion,we demonstrated a smart hybrid alginate hydrogel from which entrapped small molecules were rapidly released through UV light irradiation. The hybrid gel was prepared based on a semi-IPN structure composed of a crosslinked β-CD-grafted alginate and interpenetrating Az-PEG. In addition to crosslinking with the carboxylates along the alginate backbone induced by Ca2+ ions, the additional junctions formed by the host-guest complex between β-CD and trans-Az provided multiple photoresponsive sites within the bulk gel system. UV light irradiation induced efficient trans-to-cis photoisomerization,leading to the dissociation of the cis-Az from β-CD. Moreover,this photosensitive behavior was accompanied by substantial structural degradation of the hybrid gel,enabling the rapid release of entrapped molecules. Because biocompatible alginate hydrogels are widely applied in tissue engineering, in vitro and in vivo biological study of the applications of this photoresponsive hybrid gel in wound healing is currently being conducted.

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