幾丁聚醣與褐藻酸鈉其交聯物製成之多孔性支架緩慢釋放已酮可可鹼 之抗發炎效果

The Effects of Controlled Release of Pentoxifylline from Crosslinked Chitosan and Alginate Porous Scaffolds in Suppressing Inflammatory Reactions

邱欣洋(Sin-Yang Ciou)

指導教授 ： 林忻怡

國立臺北科技大學/工程學院/生物科技研究所/碩士(2009年)

摘要

本研究主要在利用幾丁聚醣 ( CS ) 與褐藻酸鈉 ( A ) 研發出適合用於緩慢傳送藥物的多孔性支架並與抗發炎藥物 ( 已酮可可鹼 ) 結合，並探討抗發炎之功效。將交聯形成之複合高分子製成四組多孔性支架：1.幾丁聚醣 ( CS )；2.幾丁聚醣與褐藻酸鈉交聯 ( CSA )；3.幾丁聚醣、褐藻酸鈉經氯化鈣交聯( CSACa )；4.褐藻酸鈉經氯化鈣交聯 ( ACa )。製作出之支架再進行物理性質測試與體外細胞抗發炎之實驗。由紅外線光譜觀察得知，CS的胺基與A上羧酸基交聯產生離子吸引，形成混合型吸收波峰，A中的羧酸基因受到鈣離子吸引，使的羧酸基吸收峰轉移到較高波長，鈣離子同樣會影響CSA之交聯物，均為有效交聯，再以掃描式電子顯微鏡觀察發現，經交聯的支架可使孔洞結構更為緊密；因此在壓縮結果分析，CSACa交聯複合物大幅提高抗壓強度並可減少降解程度。此外，在接觸角結果顯示，CS與A交聯後親水性增加，但CSA經氯化鈣交聯後較原支架疏水性提高；由於CS經交聯後對多孔性支架結構及親水性的改變，交聯後支架膨潤率較低。其上述因素皆會影響藥物釋放之程度，結果顯示，CSACa支架釋放藥物的速率顯著的較其他三組低。因此，幾丁聚醣與褐藻酸鈉多孔性支架確實可藉由交聯方式，有效延長藥物輸送的時間。另外，在細胞相容性實驗中顯示，幾丁聚糖與褐藻酸鈉其交聯物支架都具備有良好的細胞適應性；經LPS刺激RAW264.7細胞與多孔支架緩慢釋放PTX共同培養，測試其分泌的TNF-α及IL-6作為細胞發炎反應的指標。結果證實經培養6及24小時後，支架緩慢釋放PTX皆可達到較佳的抗發炎效果，CSACa釋放之PTX為四組中最持久，其抑制發炎因子效果較另三組為佳，可有效增強抑制發炎反應。

關鍵字

幾丁聚醣 ； 褐藻酸 ； 藥物釋放 ； 抗發炎

並列摘要

The purpose of this research was to develop a crosslinked chitosan ( CS ) and aliginate ( A ) porous scaffold that can be suitable for controlled drug release. Four materials made porous scaffolds were 1. chitosan ( CS ) , 2. chitosan crosslinked with alginate ( CSA ) , 3. chitosan crosslinked with alginate and Ca2+ ( CSACa ) , and 4. alginate crosslinked with Ca2+ ( ACa ). Esperiments performed on the crosslinked materials and scaffolds that physical properties were examined and in vitro effects of anti-inflammatory. The FTIR results showed Amide bonds were formed between CS and A because of the ionic attraction between NH3+ and COO-. Also, the ionic bonding between calcium ion and the alginate carbonyl group shifted the carboxyl peak to higher wavenumber. The calcium ion also effectively bonded to the COO- and improved the CSA mixture crosslinking. SEM showed CS crosslinked with A scaffold had smaller pores and more compact structure. CS hybrid scaffolds had stronger mechanical property ( higher Young’s modulus ) and less susceptible to enzymatic degradation than CS scaffolds. The hydrophilicity of CS increased after it was crosslinked with alginate. However, after crosslinked with Ca2+ the hydrophilicity of CSA decreased. Scaffolds made of CS crosslinked with A that change scaffold mechanical and hydrophilicity had less swell ratio than CS scaffolds. The release rate of PTX of CSACa slowest compared with the others groups. When the four groups of scaffolds were loaded with PTX and cultured with lipopolysaccharide-activated macrophages, the CSACa group had the best results in suppressing the release of inflammatory factors ( TNF-α and IL-6 ) after 6 and 24 hours. The slow PTX release from the CSACa scaffolds was thought to be the reason that improved the anti-inflammatory effect of PTX. We have successfully developed a tissue engineered scaffold that could not only used in controlled release but also has more effectively suppress inflammation.

並列關鍵字

Chitosan ； Alginate ； Drug release ； Anti-inflammatory

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