Pulkkinen Mika, Malin Minna, Tarvainen Tommy, Saarimäki Tiina, Seppälä Jukka, Järvinen Kristiina
Department of Pharmaceutics, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland.
Eur J Pharm Sci. 2007 Jun;31(2):119-28. doi: 10.1016/j.ejps.2007.03.001. Epub 2007 Mar 12.
The aim of the study was to develop enzyme sensitive polymers for pharmaceutical applications. Thus, 2,2'-bis(2-oxazoline)-linked poly-epsilon-caprolactone (PCL-O) polymers were synthesized by using epsilon-caprolactone precursors with different molecular weights (M(n): 1500, 3900, 7500 and 12,000g/mol), and the effects of PCL block length on enzymatic degradation and erosion (weight loss) of PCL-O films were studied. Solvent cast PCL and PCL-O films were incubated (22 days) in the presence of pancreatin (1%, pH 7.5), with and without enzyme inhibitors. In the absence of enzyme inhibitors, surface erosion of the PCL-O films occurred during incubation, and the erosion of the PCL-O films increased in parallel with a decrease in the PCL block length. The presence of the lipase inhibitors, paraoxon-ethyl and tetrahydrolipstatin delayed the weight loss of the PCL-O films. These results indicate that lipase was mainly responsible for the enzymatic erosion of the PCL-O films. In comparison, practically no weight loss of the PCL or the PCL-O films was observed in phosphate buffer (pH 7.4) (28 days incubation). The results demonstrate that the studied epsilon-caprolactone based poly(ester-amide)s are enzyme sensitive polymers whose erosion rate can be controlled by the PCL block length.
该研究的目的是开发用于药物应用的酶敏感聚合物。因此，通过使用不同分子量（M(n)：1500、3900、7500和12,000 g/mol）的ε-己内酯前体合成了2,2'-双（2-恶唑啉）连接的聚ε-己内酯（PCL-O）聚合物，并研究了PCL嵌段长度对PCL-O薄膜酶促降解和侵蚀（失重）的影响。将溶剂浇铸的PCL和PCL-O薄膜在有和没有酶抑制剂的情况下于胰酶（1%，pH 7.5）存在下孵育（22天）。在没有酶抑制剂的情况下，孵育期间PCL-O薄膜发生表面侵蚀，并且PCL-O薄膜的侵蚀随着PCL嵌段长度的减少而平行增加。脂肪酶抑制剂对氧磷乙酯和四氢脂抑素的存在延迟了PCL-O薄膜的失重。这些结果表明脂肪酶是PCL-O薄膜酶促侵蚀的主要原因。相比之下，在磷酸盐缓冲液（pH 7.4）中孵育28天几乎未观察到PCL或PCL-O薄膜的失重。结果表明，所研究的基于ε-己内酯的聚（酯-酰胺）是酶敏感聚合物，其侵蚀速率可通过PCL嵌段长度来控制。
