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

Zhu，Minze1; Whittaker，Andrew K.2,3; Jiang，Xingyu4,5; Tang，Rupei6; Li，Xuanyu4; Xu，Weizhi7; Fu，Changkui2,3; Smith，Maree T.7; Han，Felicity Y.2,7

2020-10-01

10.1007/s11095-020-02939-0

PHARMACEUTICAL RESEARCH   影响因子和分区

0724-8741

1573-904X

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.

bulk eroding polymers drug delivery intractable neuropathic pain intrathecal (i.t.) injection surface eroding polymers

SCI

英语

其他

National Health and Medical Research Council (NHMRC) Grant[APP1107723] ; Australian Research Council[LE0775684][LE110100028][LE110100033][LE140100087][LE160100168]

Chemistry ; Pharmacology & Pharmacy

Chemistry, Multidisciplinary ; Pharmacology & Pharmacy

WOS:000574460500001

SPRINGER/PLENUM PUBLISHERS

PHARMACOLOGY & TOXICOLOGY

2-s2.0-85091886436

Scopus

1.School of Pharmacy,Faculty of Health and Behavioural Sciences,The University of Queensland,Brisbane,Australia
2.Australian Institute for Bioengineering and Nanotechnology,The University of Queensland,Brisbane,Australia
3.ARC Centre of Excellence in Convergent Bio Nano Science and Technology,The University of Queensland,Brisbane,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,China
7.School of Biomedical Sciences,Faculty of Medicine,The University of Queensland,Brisbane,St Lucia Campus,4072,Australia

Zhu，Minze,Whittaker，Andrew K.,Jiang，Xingyu,et al. Use of Microfluidics to Fabricate Bioerodable Lipid Hybrid Nanoparticles Containing Hydromorphone or Ketamine for the Relief of Intractable Pain[J]. PHARMACEUTICAL RESEARCH,2020,37(10).

Zhu，Minze.,Whittaker，Andrew K..,Jiang，Xingyu.,Tang，Rupei.,Li，Xuanyu.,...&Han，Felicity Y..(2020).Use of Microfluidics to Fabricate Bioerodable Lipid Hybrid Nanoparticles Containing Hydromorphone or Ketamine for the Relief of Intractable Pain.PHARMACEUTICAL RESEARCH,37(10).

Zhu，Minze,et al."Use of Microfluidics to Fabricate Bioerodable Lipid Hybrid Nanoparticles Containing Hydromorphone or Ketamine for the Relief of Intractable Pain".PHARMACEUTICAL RESEARCH 37.10(2020).