Liow Sing Shy, Dou Qingqing, Kai Dan, Karim Anis Abdul, Zhang Kangyi, Xu Fujian, Loh Xian Jun
Institute of Materials Research and Engineering (IMRE), 2 Fusionopolis Way, #08-03 Innovis, Singapore 138634.
Department of Materials Science and Engineering, National University of Singapore, 9 Engineering Drive 1, Singapore 117576, Singapore.
ACS Biomater Sci Eng. 2016 Mar 14;2(3):295-316. doi: 10.1021/acsbiomaterials.5b00515. Epub 2016 Feb 4.
In situ gel delivery systems are preferred over conventional systems due to sustained and prolonged release action of therapeutic payload onto the targeted site. Thermogel, a form of in situ gel-forming polymeric formulation, undergoes sol-gel transition after administration into the body. At room temperature, the system is an aqueous polymer solution that easily entraps therapeutic payload by mixing. Upon injection, the higher physiological temperature causes gelation in situ because of the presence of thermosensitive polymers. The gel degrades gradually over time, allowing sustained release of therapeutics localized to the site of interest. This minimizes systemic toxicity and improved efficacy of drug release to the targeted site. Thermogel properties can be easily altered for specific applications via substitution and modification of components in diblock and triblock copolymer systems. The feasibility of fine-tuning allows modifications to biodegradability, biocompatibility, biological functionalization, mechanical properties, and drug release profile. This review summarized recent development in thermogel research with a focus on synthesis and self-assembly mechanisms, gel biodegradability, and applications for drug delivery, cell encapsulation and tissue engineering. This review also assessed inadequacy of material properties as a stand-alone factor on therapeutic action efficacy in human trials, with a focus on OncoGel, an experimental thermogel that demonstrated excellent individual or synergistic drug delivery system in preclinical trials but lacked therapeutic impact in human trials. Detailed analysis from all aspects must be considered during technology development for a successful thermogel platform in drug delivery and tissue engineering.
由于治疗有效载荷能在靶部位持续且长时间释放，原位凝胶递送系统比传统系统更受青睐。热凝胶是一种原位凝胶形成聚合物制剂，给药后会发生溶胶-凝胶转变。在室温下，该系统是一种聚合物水溶液，通过混合能轻松包裹治疗有效载荷。注射后，由于热敏聚合物的存在，较高的生理温度会导致原位凝胶化。凝胶会随着时间逐渐降解，使治疗药物在目标部位持续释放。这将全身毒性降至最低，并提高了药物向靶部位释放的疗效。通过对二嵌段和三嵌段共聚物系统中的成分进行取代和修饰，热凝胶的性质可轻松针对特定应用进行改变。这种微调的可行性允许对生物降解性、生物相容性、生物功能化、机械性能和药物释放曲线进行修饰。本综述总结了热凝胶研究的最新进展，重点关注合成和自组装机制、凝胶生物降解性以及在药物递送、细胞封装和组织工程中的应用。本综述还评估了材料特性作为人体试验中治疗作用疗效的单一因素的不足之处，重点关注OncoGel，这是一种实验性热凝胶，在临床前试验中显示出优异的单一或协同药物递送系统，但在人体试验中缺乏治疗效果。在药物递送和组织工程的成功热凝胶平台技术开发过程中，必须从各个方面进行详细分析。
