利用超臨界二氧化碳製備環境敏感型核殼複合物

Abstract

本實驗是利用超臨界二氧化碳，將不同的環境敏感性材料以一步合成方式結合，製備具有核殼結構的複合物顆粒，藉由反應條件控制，成功合成出具備溫度及酸鹼應答特性粉末，並分別探討其生成機制、顆粒結構型態、對環境敏感特性及實際應用於藥物載體測試。 在此，以2,2-偶氮二異丁腈做為起始劑、N,N'-亞甲基雙丙烯醯胺為交聯劑，將N-異丙基丙烯醯胺與N-乙烯基-2-吡咯酮進行共聚反應生成溫度敏感型高分子，酸鹼敏感性材料為聚二甲基矽氧烷接枝聚丙烯酸，其兩性分子可同時做為穩定劑用途。洩壓後即可得到乾燥白色粉末，減少純化產物步驟。調整操作參數(反應時間、添加單體比例、反應壓力、交聯劑量)，針對其化性、環境應答特性進行研究及探討；以傅立葉轉換紅外線光譜儀確認高分子結構、穿透式電子顯微鏡觀察複合物型態、掃描式電子顯微鏡觀察聚集情況、紫外光-可見光譜儀測量體積相變化溫度、熱重分析儀分析產物熱裂解性質，最後進行體外藥物控制釋放實驗，測試做為藥物包覆載體的可能性。 實驗結果發現產物皆為白色粉末，反應時間、壓力及交聯劑添加量會影響顆粒型態與聚集狀況，應答溫度可由調整添加親水性單體比例改變，在鹼性環境中含水能力較佳，且在適當的條件下，可達到緩慢釋放的控制效果。由於合成步驟簡單、無須分離程序，不會造成環境汙染，產物結構完整、生物可分解，膨潤吸水力佳增加藥物包覆效率，且其酸鹼及溫度敏感性質，在藥物傳輸及控制釋放領域中具有發展之潛力。

In this study, we demonstrate a one-step copolymerization to synthesis multi-responsive hydrogels with core-shell structures using scCO2 as reaction medium. In this case, N-isopropylacrylamide (NIPAM) was copolymerized with N-vinyl-2-pyrrolidinone (VPL) to form temperature-sensitive cores, and a synthetic graft copolymer, poly(dimethylsiloxane)-g-polyacrylate (PDMS-g-PAA), serves as pH-sensitive shells. PDMS-based materials, which have high chain flexibility are soluble in CO2, and offer extra properties such as physiological inertness, good blood compatibility, thermal and oxidative stability, and mechanical integrity to the composites. The assistance of PDMS-g-PAA features vitally in the process as the surfactant, which stabilizes the polymer particles sterically in the dispersion polymerization, and as the contributor of additional functionality to the final product. Therefore, the sensitivity of pH and temperature can be tuned individually. In this study, the structure of copolymers, the morphology of composites, and the influence of the impregnation of hydrophilic monomers, cross-linker concentration, reaction time, and conducting pressure are investigated. Furthermore, we examined applications in incorporation and in vitro release of drug.