School of Life Science and Biopharmaceutics, Shenyang Pharmaceutical University, Benxi, 117004, People's Republic of China.
Department of Stomatology, People's Hospital of Liaoning Province, Shenyang, 110016, People's Republic of China.
AAPS PharmSciTech. 2021 Jan 6;22(1):27. doi: 10.1208/s12249-020-01878-8.
Objective of the study was to design an injectable microsphere preparation with high drug loading of bupivacaine for prolonged release and local anesthetic. PLA or PLGA was used as the biodegradable matrix material to fabricate microspheres with the o/w emulsification-solvent evaporation method. The characterization of bupivacaine microspheres was observed by SEM, DSC, and XRPD. The microsphere preparation and extended drug release, as well as the plasma drug concentration and sciatic nerve blockade after injection of the microsphere formulation to rats were investigated. High drug-loading microspheres of more than 70% were successfully obtained with extended drug release over 5 days in vitro depending on the type of matrix and the feed ratio of drug to polymer. SEM, DSC, and XRPD results verified a novel microsphere structure characterized as the porous core composed of PLA material and form II bupivacaine crystals and dense shell formed of PLA layer. The mechanism that bupivacaine was dissolved inside the microsphere and diffused across the dense shell was suggested for drug release in vitro. The optimized PLA microsphere formulation showed low and steady plasma drug concentration over 5 days and prolonged duration of sensory and motor blockade of sciatic nerve lasted more than 3 days. Results indicated that the porous core-shell structure of PLA microsphere formulation would provide enormous potential as an injectable depot for locally prolonged delivery of bupivacaine and control of postoperative pain.
本研究的目的是设计一种布比卡因载药量高的可注射微球制剂，以实现其长效释放和局部麻醉作用。PLA 或 PLGA 被用作可生物降解的基质材料，通过 o/w 乳化-溶剂蒸发法制备微球。通过 SEM、DSC 和 XRPD 观察布比卡因微球的特征。考察了微球制剂的药物释放延长情况以及微球制剂注射到大鼠体内后的血浆药物浓度和坐骨神经阻滞情况。根据基质类型和药物与聚合物的进料比，成功获得了载药量超过 70%的高载药量微球，其体外药物释放可延长至 5 天以上。SEM、DSC 和 XRPD 结果证实了一种新型微球结构，其特征为多孔核心由 PLA 材料和 II 型布比卡因晶体组成，致密外壳由 PLA 层形成。提示了布比卡因在微球内溶解并穿过致密壳扩散的体外药物释放机制。优化的 PLA 微球制剂在 5 天内表现出低而稳定的血浆药物浓度，并且对坐骨神经感觉和运动阻滞的持续时间延长超过 3 天。结果表明，PLA 微球制剂的多孔核壳结构具有巨大的潜力，可作为布比卡因局部长期递药和控制术后疼痛的可注射储库。
