Yoshida Yasuyuki, Kawahara Keisuke, Inamoto Kenta, Mitsumune Shintaro, Ichikawa Shinya, Kuzuya Akinori, Ohya Yuichi
Department of Chemistry and Materials Engineering, Faculty of Chemistry, Materials and Bioengineering, Kansai University, 3-3-35 Yamate, Suita, Osaka 564-8680, Japan.
PREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012, Japan.
ACS Biomater Sci Eng. 2017 Jan 9;3(1):56-67. doi: 10.1021/acsbiomaterials.6b00581. Epub 2016 Nov 30.
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--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.
在室温与体温之间呈现温度响应性溶胶-凝胶转变的可生物降解注射用聚合物（IP）系统具有用于生物医学应用的潜力。然而，此类IP系统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射后于高湿条件下可能会恢复为溶胶状态。在本研究中，通过聚合物的简单混合开发了一种通过共价键形成呈现温度响应性不可逆溶胶-凝胶转变的可生物降解IP系统。制备了聚（己内酯-乙醇酸）和聚（乙二醇）的三嵌段共聚物（tri-PCG）以及在两个末端带有琥珀酰亚胺酯基团的tri-PCG（tri-PCG-SA-OSu），并将它们与水溶性多胺（通常为聚-L-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，但在温度升至37°C时30秒内呈现快速的溶胶-凝胶转变。一旦形成，水凝胶即使冷却至4°C也不会恢复为溶胶状态，因为转变时形成了共价键。浸泡在磷酸盐缓冲盐水（PBS）中的所获得的水凝胶呈现出显著更长的凝胶状态持续时间。这种呈现快速且不可逆溶胶-凝胶转变的IP系统对医学专业人员而言很方便，并且在用于药物递送系统和抗粘连材料等临床应用的生物医学装置中具有巨大的应用潜力。
