Mass Transfer Characteristics of Glutaraldehyde-crosslinked and Epoxy-crosslinked Collagen Films

戊二醛及環氧樹脂交聯之膠原蛋白薄膜質傳特性之探討

王翔郁(Shiang-Yu Wang) ； 謝玠揚(Chien-Yang Hsieh) ； 王大銘(Da-Ming Wang) ； 謝學真(Hsyue-Jen Hsieh)

《Journal of Medical and Biological Engineering》 23卷4期 (2003/12) Pp. 165-170

摘要

膠原蛋白基質為用途廣泛的生醫材料，為增強其機械強度，膠原蛋白常需以交聯劑處理來達到應用上的需求，然而膠原蛋白基質應用在藥物釋放或是組織再生方面，還須具備適當的質傳特性。在本實驗中，使用兩種常見的交聯劑－戊二醛（glutaraldehyde，簡稱GTA）以及環氧樹脂(epoxy)來改質膠原蛋白薄膜，並選用兩種藥物：theophylline（親水性藥物）及benzocaine（疏水性藥物），來探討藥物在經過交聯的膠原蛋白薄膜中質傳係數的改變。在未經處理的膠原蛋白薄膜中，theophylline和benzocaine的外顯質傳係數(D(下标 app))分別約為1×10^(-6)平方公分/s及3×10^(-7)平方公分/s。經過GTA或是epoxy交聯的膠原蛋白薄膜，兩種藥物在其中的外顯質傳係數都降低為原值的三分之一左右。另外，經過交聯劑處理的薄膜，膨澎潤度也降低，約只有未經處理薄膜膨潤度的50%。由結果顯示，經過交聯的膠原蛋白薄膜因為膠原蛋白分子間的鍵結增加，膠原蛋白薄膜的膨潤度降低，造成質傳阻力增加，所以藥物在薄膜中的外顯質傳係數減少。另外，與親水性藥物如theophylline相較，疏水性藥物如benzocaine在膠原蛋白薄膜中的通透性相對較低。

關鍵字

膠原蛋白薄膜 ； 交聯 ； 藥物通透性 ； 質傳

並列摘要

Collagen is a broadly used biomaterial and its mechanical strength can be enhanced by many crosslinking agents. Collagen matrices for drug delivery or tissue regeneration, however, are expected to have desired mass transfer characteristics. In this study, collagen films were crosslinked by two commonly used crossliking agents, namely glutaraldehyde (GTA) and epoxy. The mass transfer characteristics of the crosslinked collagen films were determined using theophylline (a hydrophilic drug) and benzocaine (a hydrophobic drug). The apparent diffusivities (D(subscript app)) of theophylline and benzocaine in untreated collagen films were about 1×10^(-6) cm^2/s and 3×10^(-7) cm^2/s, respectively. The crosslinking treatments caused a decline in D(subscript app) for both drugs. The D(subscript app) values of theophylline and benzocaine in GTA-crosslinked and epoxy-crosslinked films were about one third of the D(subscript app) values in the untreated films. In addition, swelling ratio of the GTA-crosslinked or epoxy-crosslinked films decreased by 50% as compared with untreated films. This study suggests that the decrease in the swelling ratio is due to the cross-linkages between collagen molecules, thereby increasing the mass transfer resistance and decreasing the D(subscript app) values. Further, as compared to the hydrophilic drugs such as theophylline, the permeation of hydrophobic drugs such benzocaine in collagen films is relatively poor.

並列關鍵字

Collagen films ； Crosslinking ； Drug permeation ； Mass transfer