Use of Microfluidics to Fabricate Bioerodable Lipid Hybrid Nanoparticles Containing Hydromorphone or Ketamine for the Re
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RESEARCH PAPER
Use of Microfluidics to Fabricate Bioerodable Lipid Hybrid Nanoparticles Containing Hydromorphone or Ketamine for the Relief of Intractable Pain Minze Zhu 1 & Andrew K. Whittaker 2,3 & Xingyu Jiang 4,5 & Rupei Tang 6 & Xuanyu Li 4 & Weizhi Xu 7 & Changkui Fu 2,3 & Maree T Smith 7 & Felicity Y Han 2,7 Received: 19 May 2020 / Accepted: 23 September 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020
ABSTRACT 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)
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11095-020-02939-0) contains supplementary material, which is available to authorized users. * Felicity Y Han [email protected] 1
School of Pharmacy, Faculty of Health and Behavioural Sciences, The University of Queensland, Brisbane, QLD, Australia
2
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane, QLD, Australia
3
ARC Centre of Excellence in Convergent Bio Nano Science and Technology, The University of Queensland, Brisbane, QLD, Australia
4
National Center for Nanoscience and Technology, Beijing, China
5
Department of Biomedical Engineering, Southern University of Science and Technology, Shenzhen, China
6
Engineering Research Centre for Biomedical Materials, Anhui University, Hefei, Anhui Province, China
7
School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, St Lucia Campus, Brisbane, QLD 4072, Australia
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.
KEY WORDS bulk eroding polymers . drug delivery . intractable neuropathic pain . intrathecal (i.t.) injection . surface eroding polymers INTRODUCTION The journey of res
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