Han Felicity Y, Whittaker Andrew K, Howdle Steven M, Naylor Andrew, Shabir-Ahmed Anjumn, Zhang Cheng, Smith Maree T
School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane QLD 4072, Australia.
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane QLD 4072, Australia.
Pharmaceutics. 2018 Dec 6;10(4):264. doi: 10.3390/pharmaceutics10040264.
Pain is inadequately relieved by escalating doses of a strong opioid analgesic such as morphine in up to 25% of patients with cancer-related severe pain complicated by a neuropathic (nerve damage) component. Hence, there is an unmet medical need for research on novel painkiller strategies. In the present work, we used supercritical fluid polymer encapsulation to develop sustained-release poly(lactic--glycolic acid) (PLGA) biodegradable microparticles containing the analgesic adjuvant drug ketamine, for injection by the intrathecal route. Using this approach with a range of PLGA co-polymers, drug loading was in the range 10⁻60%, with encapsulation efficiency (EE) of 60⁻100%. Particles were mainly in the size range 20⁻45 µm and were produced in the absence of organic solvents and surfactants/emulsifiers. Investigation of the ketamine release profiles from these PLGA-based microparticles in vitro showed that release took place over varying periods in the range 0.5⁻4.0 weeks. Of the polymers assessed, the ester end-capped PLGA5050DLG-1.5E gave the best-controlled release profile with drug loading at 10%.
在高达25%的伴有神经性（神经损伤）成分的癌症相关重度疼痛患者中，递增剂量的强效阿片类镇痛药（如吗啡）并不能充分缓解疼痛。因此，对于新型止痛策略的研究存在未满足的医疗需求。在本研究中，我们使用超临界流体聚合物包封技术，开发了含有镇痛辅助药物氯胺酮的聚乳酸-乙醇酸共聚物（PLGA）可生物降解缓释微球，用于鞘内注射。使用一系列PLGA共聚物采用这种方法，药物载量在10⁻60%范围内，包封率（EE）为60⁻100%。微球主要尺寸范围为20⁻45 µm，并且是在无有机溶剂和表面活性剂/乳化剂的情况下制备的。对这些基于PLGA的微球体外氯胺酮释放曲线的研究表明，释放在0.5⁻4.0周的不同时间段内发生。在所评估的聚合物中，酯封端的PLGA5050DLG-1.5E具有最佳的控释曲线，药物载量为10%。
