Key Laboratory of Drug Targeting and Drug Delivery System Ministry of Education, West China School of Pharmacy, Sichuan University, No. 17, Section 3, South Renmin Road, Chengdu, 610041, People's Republic of China.
Pharm Res. 2013 Apr;30(4):1077-85. doi: 10.1007/s11095-012-0944-9. Epub 2012 Dec 7.
PHBHHx (poly(3-hydroxybutyrate-co-3-hydroxyhexanoate)) is an excellent biomaterial for tissue repair. Here, we aim to develop a PHBHHx-based three-dimensional (3D) scaffold system for sustained delivery of proteins (insulin serves as a model protein).
The insulin-phospholipid complex (INS-PLC) was prepared to enhance the insulin lipophilicity. INS-PLC loaded PHBHHx 3D scaffolds (INS-PLC-SCAs) containing PEG-2000 were fabricated by lyophilization. In vitro release was performed in the medium with or without lipase. The bioactivity of INS-PLC-SCAs was measured in diabetic rats.
In vitro release shows that the release rate of INS-PLC-SCAs was very slow (~6% of total insulin was released within 120 days), and PEG-2000 or lipase had no effect on its release pattern. The bioactivity test shows that the hypoglycaemic effect of insulin was maintained after formulated into scaffolds. After subcutaneous (s.c.) implantation, its therapeutic effect lasted for over 130 h, and its bioavailability was enhanced by 4-fold.
PHBHHx based 3D scaffold has a great potential for sustained delivery of proteins, especially growth factors. When growth factors are incorporated, it can serve as a bifunctional system that provides a porous skeleton for cells attachment and proliferation, as well as a matrix for long term release of the loaded growth factors.
PHBHHx（聚（3-羟基丁酸酯-co-3-羟基己酸酯））是一种用于组织修复的优秀生物材料。在这里，我们旨在开发一种基于 PHBHHx 的三维（3D）支架系统，用于持续输送蛋白质（胰岛素作为模型蛋白）。
制备胰岛素-磷脂复合物（INS-PLC）以提高胰岛素的亲脂性。通过冷冻干燥制备负载胰岛素的 PHBHHx 3D 支架（含有 PEG-2000 的 INS-PLC-SCA）。在有或没有脂肪酶的介质中进行体外释放。在糖尿病大鼠中测量 INS-PLC-SCA 的生物活性。
体外释放表明 INS-PLC-SCA 的释放速率非常缓慢（在 120 天内仅释放了约 6%的总胰岛素），PEG-2000 或脂肪酶对其释放模式没有影响。生物活性测试表明，胰岛素在制成支架后仍保持降血糖作用。皮下（s.c.）植入后，其治疗效果持续超过 130 小时，生物利用度提高了 4 倍。
基于 PHBHHx 的 3D 支架具有持续输送蛋白质（特别是生长因子）的巨大潜力。当生长因子被掺入时，它可以作为一种双功能系统，为细胞附着和增殖提供多孔骨架，并为负载生长因子的长期释放提供基质。
