摘要
部分两亲性嵌段共聚物的水溶液随温度升高呈现可逆的溶胶-凝胶转变.如果转变温度介于室温和体温之间,该类体系可以在室温或更低温与药物或细胞混合,并可以注射;一旦注射进入体内,在体温下原位凝胶化,可以自动包裹药物或细胞,且该过程不依赖于化学反应.由聚乙二醇和疏水的可降解聚酯构成的嵌段共聚物的水体系在合适分子量等条件下具备以上的可逆热致凝胶化特性,成为一类极有前景的新型生物医用材料,但其中仍有大量的高分子科学问题需要解决.作者课题组十余年来在可注射热致水凝胶领域开展了系统研究:发现了聚酯-聚醚嵌段共聚物的端基效应、分子量分布效应等重要现象,总结了热致水凝胶分子设计的规律;揭示了物理凝胶化的机理,并显著扩展了可热致凝胶化聚合物的成分范围;发展了热致水凝胶面向医学应用的新策略.本专论主要以近年来复旦大学生物医用材料课题组对聚乙二醇/聚酯类可注射性热致水凝胶体系的研究为重点,介绍该类高分子材料的物理凝胶化机理和调控规律,并根据相关动物实验结果展示其潜在的临床应用前景.
Some amphiphilic copolymers in water can undergo a reversible sol-gel transition upon heating. If the transition temperature lies between room temperature and body temperature, the aqueous system can be readily mixed with drugs or cells at room temperature, and the mixture is injectable; the injected formulation is physically gelled at body temperature, and the gelation is free of any chemical crosslinking. This affords an amazing biomaterial type, yet many questions are open in light of fundamental research and potential clinical applications. In particular, block copolymers composed of hydrophilic poly（ethylene glycol） （PEG） and some hydrophobic biodegradable polyesters such as poly（lactide-co-glycolide） （PLGA） are of great clinical potential, yet of very unclear physical crosslinking points. This feature article summarizes the corresponding extensive investigations in the authors＇ group led by Ding at Fudan University for a decade. The Ding group has found the significant effects of the end groups of the copolymer, molar mass dispersity DM, and other molecular parameters on thermogellability, and revealed the corresponding rules of molecular design, based on their polymer chemistry studies. For instance, with increase in DM under either given number average or weight average molecule weight, the sol-gel transition temperature for some block copolymer aqueous systems could shift unidirectionally, which indicates that the effect of molecular weight distribution could not be interpreted simply from addition of the effects of molecular weight or DM affords an independent adjustable parameter. The Ding group has shed light on the mechanism of their thermogelling by putting forward the model of percolated micelle network to describe the internal structure of the physical hydrogel, and extended the range of the thermogellable molecular composition of the copolymers to a large extent by establishing a blend strategy, based on their polymer physics studies. The Ding group have also put forward many strategies for the clinical applications of the thermogels using animal models, including prevention of postoperative tissue adhesion, submucosal cushion for endoscopic submucosal dissection, sustained release carriers of antitumor drugs such as camptothecin derivatives, long-acting formulations of polypeptide drugs such as exenatide in treatment of type II diabetes, and tissue engineering of cartilage. The Ding group has also laid a material basis towards potential products of medical devices and drug carriers including the appropriate way of sterilization and improvement of the handling property of the synthesized polymers. The Ding group suggest some perspectives in the end of this feather article.
作者
崔书铨
俞麟
丁建东
Shu-quan Cui;Lin Yu;Jian-dong Ding(State Key Laboratory of Molecular Engineering of Polymers,Department of Macromolecular Science,Fudan University,Shanghai 20043)
出处
《高分子学报》
SCIE
CAS
CSCD
北大核心
2018年第8期997-1015,共19页
Acta Polymerica Sinica
基金
国家自然科学基金(基金号21774024
51533002)
国家重点研发计划项目(项目号2016YFC1100300)资助
