School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, QLD, Australia; Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, QLD, Australia.
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, QLD, Australia.
Int J Pharm. 2020 May 15;581:119291. doi: 10.1016/j.ijpharm.2020.119291. Epub 2020 Apr 4.
Ketamine in sub-anaesthetic doses is an analgesic adjuvant with a morphine-sparing effect. Co-administration of a strong opioid with an analgesic adjuvant such as ketamine is a potential treatment option, especially for patients with cancer-related pain. A limitation of ketamine is its short in vivo elimination half-life. Hence, our aim was to develop biocompatible and biodegradable ketamine-loaded poly(ethylene glycol) (PEG)-block-poly(lactic-co-glycolic acid) (PLGA) nanoparticles for sustained release. Ketamine-encapsulated single polymer PEG-PLGA nanoparticles and double polymer PEG-PLGA/shellac (SH) nanoparticles with a high drug loading of 41.8% (drug weight/the total weight of drug-loaded nanoparticles) were prepared using a new sequential nanoprecipitation method. These drug-loaded nanoparticles exhibited a sustained-release profile for up to 21 days in vitro and for more than 5 days after intravenous injection in mice. Our study demonstrates that high drug loading and a sustained release profile can be achieved with ketamine-loaded PEG-PLGA nanoparticles prepared using this new nanoprecipitation method.
亚麻醉剂量的氯胺酮是一种具有吗啡节省效应的镇痛佐剂。联合使用强阿片类药物和镇痛佐剂（如氯胺酮）是一种潜在的治疗选择，特别是对于癌症相关疼痛的患者。氯胺酮的一个限制是其体内消除半衰期短。因此，我们的目标是开发生物相容性和可生物降解的载有氯胺酮的聚乙二醇（PEG）-嵌段-聚（乳酸-共-乙醇酸）（PLGA）纳米粒，以实现其持续释放。采用一种新的顺序纳米沉淀法，制备了载有氯胺酮的单聚合物 PEG-PLGA 纳米粒和双聚合物 PEG-PLGA/紫胶（SH）纳米粒，其载药量高达 41.8%（药物重量/载药纳米粒的总重量）。这些载药纳米粒在体外可长达 21 天持续释放，在小鼠体内静脉注射后可超过 5 天持续释放。本研究表明，使用这种新的纳米沉淀法可以制备载有氯胺酮的 PEG-PLGA 纳米粒，实现高载药量和持续释放。
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