中孔洞二氧化鈦薄膜的合成與分析及其藥物釋放研究

Abstract

本論文利用三區塊高分子當作有機模板，經揮發誘導自組裝 (evaporation-induced self-assembly, EISA) 原理，藉由調控基板種類、老化溫度、熱處理條件等成功合成出中孔洞二氧化鈦薄膜，且利用中孔洞二氧化鈦薄膜作為藥物載體，探討薄膜藥物釋放行為、生物相容性、生物活性。 由實驗結果發現，合成態薄膜塗佈在矽晶片時形成大範圍有序 (long-ranged order) 的六角對稱介穩結構 (mesophase)，且利用Ibuprofen分子的添加，加強合成液介穩結構的形成；當老化溫度從室溫增加到80℃時，微胞由六角堆積排列轉變成層狀排列，發生微胞相轉換現象 (phase transformation) 。另外，合成態薄膜經過50℃老化處理後，再經過450℃煅燒可形成具熱穩定性的蟲型孔洞 (wormhole-like) 結構。利用煅燒後薄膜調控含浸藥物方式、藥物的濃度及藥物分子尺寸，結果顯示Ibuprofen分子能有效擴散進孔洞內部且有長達30小時的藥物釋放行為。此外，煅燒後的中孔洞二氧化鈦薄膜，具有銳鈦礦相 (anatase) 結構，有助於骨細胞的貼附與成長；由模擬人體液 (SBF) 浸泡7天後，有明顯磷灰石沉積現象，說明薄膜具很好的生物活性。

Evaporation-induced self-assembly mesoporous TiO2 thin film was prepared by using amphiphilic triblock copolymer as a template under acidic conditions. Synthetic parameters such as different substrates, aging temperature, and heat treatment were used to characterize the resulting TiO2 mesostructure. Experimental results showed that the as-synthesized TiO2 thin film by spin-coating on silicon wafer formed a long-ranged order hexagonal mesophase. Ibuprofen, an anti-inflammatory drug, was encapsulated upon film synthesis which unexpectedly showed a considerable improvement in the orderliness of the mesophase. Controlled aging temperature from room temperature to 80℃ caused a change of micellar structure of the soft template molecule from hexagonal to lamellar configuration. To maintain the mesoporous network in the TiO2 phase, it is necessary to age the film for a suitable time period before calcination. The resulting mesoporous TiO2 thin film showed a wormhole-like structure upon calcination at 450℃. For drug delivery study, it was found that the release behavior of the drugs can be altered by using different drug impregnation conditions, different drug concentrations, and drugs with various molecular size. After calcination at 450℃, the anatase mesoporous TiO2 thin film can stimulate osteoblast adhesion and induce bone-like apatite formation in vitro, indicating that the multifunctional advantages of such a bioactive, drug-incorporated mesoporous TiO2 thin film for clinical practices are highly expected.