THERMALLY ON OFF SWITCHING POLYMERS FOR DRUG PERMEATION AND RELEASE
THERMALLY ON OFF SWITCHING POLYMERS FOR DRUG PERMEATION AND RELEASE
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DOI：
10.1016/0168-3659(90)90138-j
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发表时间：
1990-01-01
影响因子：
10.8
通讯作者：
KIM, SW
中科院分区：
文献类型：
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作者：
OKANO, T;BAE, YH;KIM, SW
研究了交联聚N，N ′-烷基取代丙烯酰胺在水中的溶胀与外界温度变化的关系。聚合物在水中的溶胀随温度的显著变化可以归因于聚合物链的微妙的亲水/疏水平衡，并且受到取代丙烯酰胺上烷基侧链的大小、构型和流动性的影响。本文还合成了N-异丙基丙烯酰胺（IPAAm）-甲基丙烯酸丁酯（BMA）共聚物以及IPAAm/PTMEG互穿聚合物网络（IPN），并对其进行了改性研究。凝胶组合物和制造技术影响圆盘形几何形状（10 mm直径，0.7 mm厚度）随温度升高的凝胶收缩行为。这些研究中的一个重要观察结果是凝胶的初始收缩发生在膜的表面上。这种现象的结果是，外表面（皮肤）形成了一个致密的结构，相比，大部分的膜，调节水和随后的溶质transmitt.To评估这些“热敏”网络的控制释放方面，吲哚美辛（模型药物）的解决方案加载到设备。吲哚美辛从凝胶中的释放与所观察到的溶胀性质相关。在低温下，吲哚美辛遵循伪零级或一级释放动力学，这取决于基质，而在高温下吲哚美辛未能扩散出凝胶。这种响应于温度的“开-关“释放限于窄的温度范围。在每个温度循环的低温区域中的滞后时间和释放曲线受共聚物或IPN的组成的影响。此外，胰岛素和葡萄糖通过同一膜的渗透表现出响应于温度的类似的开关机制。
The swelling of crosslinked poly(N,N'-alkyl substituted acrylamides) in water was studied in relation to changes in external temperature. The significant swelling changes of the polymer in water in response to temperature can be attributed to the delicate hydrophilic/hydrophobic balance of the polymer chain, and was affected by the size, configuration and mobility of the alkyl side chains on the substituted acrylamides. Sharp swelling transitions may occur at an optimum hydrophilic/hydrophobic balance and was found only inN-isopropylacrylamide network, among the tested networks.Copolymers including crosslinked poly(N-isopropylacrylamide (IPAAm)-co-butylmethacrylate (BMA)) and interpenetrating polymer networks (IPNs) of poly(IPAAm) and poly tetramethylene ether glycol (PTMEG) were also synthesized and investigated as modified IPAAm networks. The gel shrinking behavior for a disk-shaped geometry (10 mm diameter, 0.7 mm thickness) with increasing temperature was affected by the gel composition and fabrication techniques. An important observation in these studies was that the initial shrinkage of the gel occurred on the surface of the membrane. The consequence of this phenomenon was that the outer surface (skin) formed a denser structure, as compared to the bulk of the membrane, which regulated water and subsequently solute transport.To evaluate the controlled release aspects of these “thermosensitive” networks, indomethacin (a model drug) was solution loaded into the devices. The release of indomethacin from the gels correlated with the observed swelling properties. At low temperature, indomethacin followed pseudo-zero-order or first-order release kinetics, depending on the matrices, while at elevated temperatures indomethacin failed to diffuse out of the gels. This “on-off ” release in response to temperature was restricted to a narrow temperature range. The lag time and release profile in the low temperature region of each temperature cycle was influenced by the composition of the copolymer or IPNs. In addition, the permeation of insulin and glucose through the same membrane demonstrated a similar on-off mechanism in response to temperature.