不同聚合溫度對熱可逆膠體之快速膨潤收縮及藥物釋放行為影響之研究

STUDIES ON THE INFLUENCE OF DIFFERENT POLY- MERIZATION METHODS ON FAST SWELLING- DESWELLING AND DRUG RELEASE BEHAVIORS FOR THERMOREVERSIBLE HYDROGELS

林佳盈(Chia-Ying Lin)

指導教授 ： 李文福

大同大學/工程學院/化學工程學系所/碩士(2006年)

摘要

本研究第一部份主要在討論由NIPAAm添加親水性單體(如PEGMEA和HEMA)所製備一之系列溫感性膠體其膨潤及收縮行為之研究。為了改善一般PNIPAAm膠體對溫度的反應速率，我們利用冷凍法(-20℃)來進行反應。結果顯示，添加PEGMEA和HEMA的共聚合膠體中，poly(NIPAAm/PEGMEA)膠體之快速膨潤收縮表現比poly(NIPAAm/HEMA)膠體來得好；同時，含有PEGMEA之膠體具有較快的初始膨潤速率及較高的擴散係數，但其膠體強度較含HEMA之膠體差。
由於溫感性膠體受溫度升高影響而產生膠體體積的收縮或變化，因此改善水膠對溫度的敏感性則成為研究重點。這部分研究主要是比較不同烷鏈結構對膠體收縮及膨潤之影響，因此利用不同的聚合溫度來製備一系列不同醯胺衍生物(例如：NIPAAm, NEPAAm, NTHFAAm)之溫感性膠體。反應在三個不同的溫度(-20, 25, 45℃)環境下進行。在此，我們針對水膠的膨潤動力、收縮動力、快速膨潤收縮行為及其機械性質做探討。結果顯示，不同聚合溫度會影響膠體聚合時，疏水基及親水基不同程度的堆疊與聚集，而對內部結構造成影響。同時，在45℃下製備的膠體，具有最佳的快速膨潤收縮的行為表現，但同時其膠體性質也較其他膠體來得脆弱；而在-20℃下製備的膠體，則具有較強的機械強度，同時也具有良好的膨潤及收縮性質。我們亦由實驗結果得知，快速膨潤收縮時的膨潤度差主要受到實驗時的溫度及膠體內部結構之影響
第三部份則是，利用不同的聚合溫度來製備一系列不同醯胺衍生物(例如：NIPAAm, NEPAAm, NTHFAAm)之溫感性膠體，來進行藥物釋實驗。我們使用sulfanilamide(Mw=172)，caffeine(Mw=194)及vitamin B12(Mw=1355)來進行藥物釋放實驗。結果發現，在25℃下製備之膠體比其他條件之膠體還可吸收更多的藥物，這可歸究於高於/低於LCST的溫度進行聚合，則會造成膠體結構不同程度破壞。而當以Vitamin B12進行藥物釋放實驗時，我們發現，在25℃及45℃下製備之膠體，表現出相同的藥物釋放趨勢(但不同於-20℃製備之膠體)如下：N>F>E。這可能是在低於結晶溫度下成膜，會造成不同於室溫及高溫下成膜之膠體結構之故，因此造成膠體對藥物的釋放行為表現不同。

關鍵字

冷凍法 ； 藥物釋放 ； 快速膨潤收縮 ； 溫感性 ； 膠體 ； 相分離法

並列摘要

A series of thermosensitive hydrogels were prepared from N-isopropylacrylamide (NIPAAm) and hydrophilic monomers, such as poly (ethylene glycol) methyl ether acrylate (PEGMEA) and 2-hydroxyethyl methacrylate (HEMA). The effect of hydrophilic monomer content on the swelling and deswelling behavior for the poly(NIPAAm/hydrophilic monomer) copolymeric hydrogels was investigated. To improve the slow swelling-deswelling behavior of the normal poly(NIPAAm) gel, the polymerization process was carried out by freezing method at -20℃. The results showed that the poly(NIPAAm/PEGMEA) copolymeric gels have better fast swelling-deswelling performance than the poly(NIPAAm/HEMA) gels. The results also showed that the copolymeric gels containing PEGMEA moiety had more rapid initial swelling rate and higher diffusion coefficient of water penetrated into the gels than those gels containing HEMA, but had weaker gel strength.
Thermosensitive hydrogels exhibit a response to external temperature variation and shrink in volume abruptly as the temperature is increased above their critical gel transition temperature. Improving the temperature-responsive rate of the hydrogel is always a main focus. The purpose of this study is to improve and to compare the shrinking and swelling rate of three different alkylacrylamide-derivative gels. Therefore, a series of thermosensitive hydrogels were prepared based on three different monomers, such as N-isopropyl acrylamide, (NIPAAm), 3-ethoxypropyl acrylamide, (NEPAAm), and tetrahydrofurfuryl acrylamide, (NTHFAAm). The polymerization was conducted at -20℃ (below the LCST), 25℃ (near the LCST), and 45℃ (above the LCST). The swelling kinetics, deswelling kinetics, fast swelling-deswelling behaviors, and physical properties of the gels were investigated in this study. The results suggest that the gels polymerized at different temperatures would affect the structure of the gels, resulting in different degree of aggregation of the hydrophobic or hydrophilic in the gels. The results also indicate that the gels prepared at 45℃ have weaker structure, but better swelling and deswelling performance than other gels. The gels prepared at -20℃ have stronger structure as well as good swelling and deswelling behaviors. The results also exhibit that the damping range of the swelling-deswelling ratio for the gels were mainly affected by the swelling-deswelling temperatures and structures of gels formed during polymerization at different temperatures.
A series of thermosensitve hydrogels were prepared based on three different monomers, which were N-isopropylacrylamide, (NIPAAm), 3-etho- xypropylamide, (NEPAAm), and tetrahydrofurfurylamide, (NTHFAAm). The polymerization was conducted at -20℃ (below the LCST), 25℃ (near the LCST), and 45℃ (above the LCST). Poly-(N-isopropyl acrylamide) (PNIPAAm), poly(N-ethoxypropyl acrylamide) (PNEPAAm), and poly(N-tetrahydrofurfuryl acrylamide) (PNTHFAAm) are thermosensitive polymeric matrix. The gel transition temperature or lower critical solution temperature (LCST) are about 32℃, 29℃, 25℃, for PNIPAAm, PNTHFAAm, and PNEPAAm, respectively. The influence of different polymerization temperatures on the drug release behavior on thermosensitve hydrogels has been investigated in this study. The model drugs used in the drug release tests are sulfanilamide (Mw=172), caffeine (Mw=194), and vitamin B12 (Mw=1355). We found that the gels prepared at 25℃ can absorb the largest amount of drug than those gels prepared at other two temperatures. It is due to the structure had been damaged when the polymerization is much higher/lower than the LCST. When using vitamin B12 as model drug, the gels, prepared at 25℃ and 45℃, also showed the same sequence as N>F>E, but different from gels prepared at -20℃. It maybe due to that the structure aggregation of the gel polymerized under freezing point is different, which resulted in different drug release of the gels.

並列關鍵字

drug release ； fast-responsive ； NIPAAm ； thermosensitivitive ； hydrogel ； freezing-method ； phase-separation method

參考文獻

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