College of Pharmacy and Biological Engineering, Chengdu University, Chengdu 610106, China.
Department of Nephrology, The Third People's Hospital of Chengdu, Chengdu, 610031, China.
Curr Drug Deliv. 2019;16(4):331-340. doi: 10.2174/1567201816666181119112952.
In this study, an injectable Sucrose Acetate Isobutyrate (SAIB) drug delivery system (SADS) was designed and fabricated for the sustained release of Ropivacaine (RP) to prolong the duration of local anesthesia.
By mixing SAIB, RP, and N-methyl-2-pyrrolidone, the SADS was prepared in a sol state with low viscosity before injection. After subcutaneous injection, the pre-gel solution underwent gelation in situ to form a drug-released depot.
The in vitro release profiles and in vivo pharmacokinetic analysis indicated that RP-SADS had suitable controlled release properties. Particularly, the RP-SADS significantly reduced the initial burst release after subcutaneous injection in rats.
In a pharmacodynamic analysis of rats, the duration of nerve blockade was prolonged by over 3-fold for the RP-SADS formulation compared to RP solution. Additionally, RP-SADS showed good biocompatibility in vitro and in vivo. Thus, the SADS-based depot technology is a safe drug delivery strategy for the sustained release of local anesthetics with long-term analgesia effects.
本研究设计并制备了一种可注射的蔗糖醋酸丁酸酯（SAIB）药物递送系统（SADS），以实现罗哌卡因（RP）的持续释放，从而延长局部麻醉的持续时间。
通过混合 SAIB、RP 和 N-甲基-2-吡咯烷酮，在注射前将 SADS 以低粘度的溶胶状态进行制备。皮下注射后，预凝胶溶液在原位发生胶凝，形成药物释放库。
体外释放曲线和体内药代动力学分析表明，RP-SADS 具有合适的控制释放特性。特别是，RP-SADS 显著减少了 RP 溶液皮下注射后的初始突释。
在大鼠药效学分析中，与 RP 溶液相比，RP-SADS 制剂使神经阻滞持续时间延长了 3 倍以上。此外，RP-SADS 在体外和体内均表现出良好的生物相容性。因此，基于 SADS 的储库技术是一种安全的药物递送策略，可用于局部麻醉剂的持续释放，具有长期的镇痛效果。
