Rao Zi-Kun, Chen Rui, Zhu Hong-Yu, Li Yang, Liu Yu, Hao Jian-Yuan
School of Microelectronics and Solid-State Electronics, University of Electronic Science and Technology of China, No.4, Section 2, North Jian'she Road, Chengdu 610054, China.
Materials (Basel). 2018 Feb 26;11(3):338. doi: 10.3390/ma11030338.
To improve the release profile of peptide drugs, thermos-responsive triblock copolymer poly (ε-caprolactone-co-p-dioxanone)-b-poly (ethylene glycol)-b-poly (ε-caprolactone-co-p-dioxanone) (PECP) was prepared and end capped by succinic anhydride to give its carboxylic terminated derivative. Both PCEP block copolymer and its end group modified derivative showed temperature-dependent reversible sol-gel transition in water. The carboxylic end group could significantly decrease the sol-gel transition temperature by nearly 10 °C and strengthen the gel due to enhanced intermolecular force among triblock copolymer chains. Furthermore, compared with the original PECP triblock copolymer, HOOC-PECP-COOH copolymer displayed a retarded and sustained release profile for leuprorelin acetate over one month while effectively avoiding the initial burst. The controlled release was believed to be related to the formation of conjugated copolymer-peptide pair by ionic interaction and enhanced solubility of drug molecules into the hydrophobic domains of the hydrogel. Therefore, carboxyl terminated HOOC-PECP-COOH hydrogel was a promising and well-exhibited sustained release carrier for peptide drugs with the advantage of being able to develop injectable formulation by simple mixing.
为改善肽类药物的释放特性，制备了温敏性三嵌段共聚物聚（ε-己内酯-对二氧环己酮）-b-聚乙二醇-b-聚（ε-己内酯-对二氧环己酮）（PECP），并用琥珀酸酐进行封端以得到其羧基封端的衍生物。PECP嵌段共聚物及其端基修饰衍生物在水中均表现出温度依赖性的可逆溶胶-凝胶转变。羧基端基可使溶胶-凝胶转变温度显著降低近10℃，并由于三嵌段共聚物链间分子间作用力增强而强化凝胶。此外，与原始的PECP三嵌段共聚物相比，HOOC-PECP-COOH共聚物对醋酸亮丙瑞林显示出超过一个月的缓释和持续释放特性，同时有效避免了初始突释。控释被认为与通过离子相互作用形成共轭共聚物-肽对以及药物分子在水凝胶疏水区域中的溶解度增加有关。因此，羧基封端的HOOC-PECP-COOH水凝胶是一种有前景且表现良好的肽类药物缓释载体，具有能够通过简单混合开发注射制剂的优势。
