以原子轉移自由基聚合法製備溫度/酸鹼敏感型星狀聚合物及其藥物釋放應用

Preparation of thermo- and pH- sensitive star copolymers via ATRP and used in drug release application

徐淑屏(Shu-Ping Hsu)

指導教授 ： 芮祥鵬

國立臺北科技大學/工程學院/有機高分子研究所/碩士(2014年)

摘要

本研究利用原子轉移自由基聚合法成功合成出具有溫敏/酸鹼敏感型星狀聚合物，而研究目的在評估其作為藥物載體的可行性。合成分兩步驟進行，β-環糊精與2-溴丙酰溴行酯化取代反應，可得末端18.74個溴化物之核起劑，再利用此起始劑與溫敏單體NIPAAm和酸鹼型單體IAM以原子轉移自由基聚合法共聚合得星狀聚合物。
結果顯示，星狀共聚物相變化溫度隨IAM莫爾比例增加而溫度提高，共聚物在較低的重量百分比濃度及鹼性環境下，相變化溫度有提高趨勢；動態光散射儀觀察(DLS)到隨溫度上升粒子有縮小的情況，其大小約104nm至208nm，也發現隨環境pH值增加，共聚物鏈上弱酸基團被質子化，導致粒徑呈現較澎潤狀態。經由穿透式電子顯微鏡(TEM)影像顯示有加入IAM之共聚物會自組裝呈現核-殼分明圓形結構。藥物釋放實驗中，我們在四種不同環境條件下觀察，pH7.4及37℃環境下，含藥的聚合物整體累積釋放效果最佳，表示此載體可抵抗酸性環境下攻擊，能在人體腸道環境得到良好吸收，同時，證實此載體具有溫度及酸鹼敏感性，成為新型具雙重刺激反應功能型的藥物載體。

關鍵字

溫度/pH值敏感型高分子 ； 聚異丙基丙烯醯胺 ； 原子轉移自由基聚合法 ； 最低臨界溶液溫度

並列摘要

The goal of this study is to evaluate if the star-copolymers have the potential for oral drug delivery system. We synthesized thermo- and pH- sensitive star copolymers, a star-poly(NIPAAm-co-IAM) with β-cyclodextrin (β-CD) produced by atom transfer radical polymerization (ATRP), in which the esterification of β-CD hydrodyl groups reaction with 2-bromopropionyl bromide produce β-CD-core initiator with 18.74 initiation sites.
The results indicates that the LCST values of star copolymers increased as hydrophilic monomer feed molar ratio of IAM, having increased lower copolymer content in water media and higher pH value. By DLS measurement observation, it was found the particle becomes a smaller size with increasing temperature, in which diameters were about 104-208nm. It was also found that the size of the micelles increased with the pH values increasing. This is probably due to the ionization of carboxyl groups of the IAM segment with high pH value. The TEM images revealed that the morphology of micelle can self-assemble into core-shell spherical structure of copolymer within IAM. The drug release experiment were conducted under four different environment conditions, observed at pH7.4 and 37℃. The copolymer containing the cumulative drug release had the best overall performance, which means the carrier may be resistant to attack under acidic condition. Thus, the human digestive system will provide good absorption, confirming that the carrier has temperature- and pH- sensitive, therefore is subjective to becoming a new drug carrier with dual stimulation response function type.

並列關鍵字

Thermo/pH sensitive ； poly(N-isopropylacrylamide) ； LCST

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