Liu Yandi, Sunderland V Bruce, O'Neil A George
School of Pharmacy, Curtin University of Technology, GPO BOX U 1987, Perth, WA, 6845, Australia.
Drug Dev Ind Pharm. 2006 Jan;32(1):85-94. doi: 10.1080/03639040500388466.
The aim of this study was to prepare poly(d, l-lactide) (PLA) microspheres containing naltrexone (NTX) by a solvent evaporation method, and to evaluate both in vitro and in vivo release characteristics and histopathological findings of tissue surrounding an implant formulation in rats. This method enabled the preparation of microspheres of regular shape and relatively narrow particle size distribution. The in vitro release profiles of NTX from PLA microspheres showed the release of NTX did not follow zero-order kinetics. An initial burst release was observed, subsequently followed by a nearly constant rate of 0.4% per day after ten days. The cumulative amount of NTX released at the end of 60 days was 80%. Compressed microspheres showed near zero-order sustained release of NTX for 360 days. The plasma NTX levels in rats showed that for compressed microspheres NTX concentrations were constant and exceeded 2 ng/mL for 28 days. Throughout the 28 days of study, the implantations cause a minor inflammatory response, which can be regarded as a normal defence mechanism. The sustained release performance of NTX from the biodegradable depot systems may provide a reliable, convenient, and safe mechanism for the administration of NTX for the long-term treatment of opioid dependence.
本研究的目的是通过溶剂蒸发法制备含纳曲酮（NTX）的聚（d，l-丙交酯）（PLA）微球，并评估其体外和体内释放特性以及大鼠体内植入制剂周围组织的组织病理学发现。该方法能够制备形状规则且粒径分布相对较窄的微球。PLA微球中NTX的体外释放曲线表明，NTX的释放不遵循零级动力学。观察到有初始突释现象，随后在十天后释放速率几乎恒定，每天为0.4%。60天结束时NTX的累积释放量为80%。压制微球显示NTX近零级持续释放360天。大鼠体内血浆NTX水平表明，压制微球的NTX浓度恒定，在28天内超过2 ng/mL。在整个28天的研究过程中，植入引起轻微的炎症反应，这可被视为一种正常的防御机制。NTX从可生物降解长效制剂系统中的持续释放性能可能为NTX用于阿片类药物依赖的长期治疗提供一种可靠、方便且安全的给药机制。
