Biodegradable Injectable Polymer Systems Exhibiting Temperature-Responsive Irreversible Sol-to-Gel Transition by Covalent Bond Formation.
Biodegradable Injectable Polymer Systems Exhibiting Temperature-Responsive Irreversible Sol-to-Gel Transition by Covalent Bond Formation.
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DOI：
10.1021/acsbiomaterials.6b00581
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发表时间：
2017-01
影响因子：
5.8
通讯作者：
Y. Yoshida;Keisuke Kawahara;Kentaro Inamoto;Shintaro Mitsumune;S. Ichikawa;A. Kuzuya;Y. Ohya
中科院分区：
文献类型：
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作者：
Y. Yoshida;Keisuke Kawahara;Kentaro Inamoto;Shintaro Mitsumune;S. Ichikawa;A. Kuzuya;Y. Ohya
可生物降解的可注射聚合物（IP）系统在室温和体温之间表现出温度响应性溶胶-凝胶转变，具有用于生物医学应用的潜力。然而，这种IP体系的凝胶化是通过物理交联的可逆过程，并且由此形成的水凝胶在注入后在高度润湿的条件下可能恢复到溶胶状态。在这项研究中，一个可生物降解的IP系统表现出温度响应的不可逆的溶胶-凝胶转变通过共价键形成的聚合物的简单混合开发。制备聚（己内酯-共-乙醇酸）和聚（乙二醇）的三嵌段共聚物（三-PCG）和在两个末端具有连接的琥珀酰亚胺酯基团的三-PCG（三-PCG-SA-OSu），并与水溶性多胺（通常为聚-1-赖氨酸）混合在一起。所获得的IP制剂在混合后处于溶胶状态，但在将温度升高至37 °C时在30秒内表现出快速的溶胶至凝胶转变。一旦形成，水凝胶即使在冷却至4 °C后也不会恢复到溶胶状态，因为在转变时形成共价键。浸泡在磷酸盐缓冲盐水（PBS）中的所得水凝胶表现出显著更长的凝胶状态持续时间。该IP系统表现出快速和不可逆的溶胶-凝胶转变，便于医疗专业人员使用，并具有用于临床应用的生物医学设备，如药物输送系统和抗粘附材料的巨大潜力。
Biodegradable injectable polymer (IP) systems exhibiting temperature-responsive sol-to-gel transitions between room temperature and body temperature have the potential for use in biomedical applications. However, gelation of such IP systems is a reversible process through physical cross-linking, and the hydrogels thus formed are likely to revert to the sol state under highly wet conditions after injection. In this study, a biodegradable IP system exhibiting temperature-responsive irreversible sol-to-gel transition by covalent bond formation was developed by simple mixing of polymers. A triblock copolymer of poly(caprolactone-co-glycolic acid) and poly(ethylene glycol) (tri-PCG) and tri-PCG with attached succinimide ester groups at both termini (tri-PCG-SA-OSu) were prepared and mixed together with a water-soluble polyamine (typically poly-l-lysine). The obtained IP formulation was in the sol state after mixing, but exhibited a rapid sol-to-gel transition within 30 s upon increasing the temperature to 37 °C. Once formed, the hydrogel did not revert to the sol state, even after cooling to 4 °C, because of the formation of covalent bonds upon transition. The obtained hydrogel soaked in phosphate buffered saline (PBS) exhibited a significantly longer duration time of the gel state. This IP system exhibiting a rapid and irreversible sol-to-gel transition is convenient for medical professionals and possesses great potential for use in biomedical devices for clinical applications such as drug delivery systems and antiadhesive materials.