Use of Microfluidics to Fabricate Bioerodable Lipid Hybrid Nanoparticles Containing Hydromorphone or Ketamine for the Relief of Intractable Pain

• Published in: Pharmaceutical research Vol. 37; no. 10; p. 211
• Main Authors: Zhu, Minze, Whittaker, Andrew K., Jiang, Xingyu, Tang, Rupei, Li, Xuanyu, Xu, Weizhi, Fu, Changkui, Smith, Maree T, Han, Felicity Y
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.10.2020; Springer; Springer Nature B.V
• Subjects: Analgesia; Analgesics; Analysis; Biochemistry; Biomedical and Life Sciences; Biomedical Engineering and Bioengineering; Biomedicine; Care and treatment; Injection; Ion channels; Ketamine; Light scattering; Medical Law; Microfluidics; Nanoparticles; Narcotics; Opioids; Pain; Pain perception; Peripheral neuropathy; Pharmacology/Toxicology; Pharmacy; Polylactide-co-glycolide; Polymers; Research Paper; Transmission electron microscopy; bulk eroding polymers; surface eroding polymers; intrathecal (i.t.) injection; drug delivery; intractable neuropathic pain
• ISSN: 0724-8741; 1573-904X; 1573-904X
• DOI: 10.1007/s11095-020-02939-0

Purpose For patients with intractable cancer-related pain, administration of strong opioid analgesics and adjuvant agents by the intrathecal (i.t.) route in close proximity to the target receptors/ion channels, may restore pain relief. Hence, the aim of this study was to use bioerodable polymers to encapsulate an opioid analgesic (hydromorphone) and an adjuvant drug (ketamine) to produce prolonged-release formulations for i.t. injection. Methods A two-stage microfluidic method was used to fabricate nanoparticles (NPs). The physical properties were characterised using dynamic light scattering and transmission electron microscopy. A pilot in vivo study was conducted in a rat model of peripheral neuropathic pain. Results The in vitro release of encapsulated payload from NPs produced with a polymer mixture (CPP-SA/PLGA 50:50) was sustained for 28 days. In a pilot in vivo study, analgesia was maintained over a three day period following i.t. injection of hydromorphone-loaded NPs at 50 μg. Co-administration of ketamine-loaded NPs at 340 μg did not increase the duration of analgesia significantly. Conclusions The two-stage microfluidic method allowed efficient production of analgesic/adjuvant drug-loaded NPs. Our proof-of-principle in vivo study shows prolonged hydromorphone analgesic for 78 h after single i.t. injection. At the i.t. dose administered, ketamine released from NPs was insufficient to augment hydromorphone analgesia.