Formulation of Bioerodible Ketamine Microparticles as an Analgesic Adjuvant Treatment Produced by Supercritical Fluid Polymer Encapsulation
by
Felicity Y. Han 1
, Andrew K. Whittaker 2,3, Steven M. Howdle 4,5, Andrew Naylor 6, Anjumn Shabir-Ahmed 5, Cheng Zhang 2,3 and Maree T. Smith 1,7,*
Felicity Y. Han 1, Andrew K. Whittaker 2,3, Steven M. Howdle 4,5, Andrew Naylor 6, Anjumn Shabir-Ahmed 5, Cheng Zhang 2,3 and Maree T. Smith 1,7,*
1
School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane QLD 4072, Australia
2
Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane QLD 4072, Australia
3
ARC Centre of Excellence in Convergent Bio Nano Science and Technology, The University of Queensland, Brisbane QLD 4072, Australia
4
School of Chemistry, University of Nottingham, Nottingham NG7 2RD, UK
5
Critical Pharmaceuticals Ltd., BioCity Nottingham, Nottingham NG1 1GF, UK
6
Upperton Limited, Biocity Nottingham, Nottingham NG7 2TN, UK
7
School of Pharmacy, Faculty of Health and Behavioural Sciences, The University of Queensland, Brisbane QLD 4072, Australia
*
Author to whom correspondence should be addressed.
Pharmaceutics 2018, 10(4), 264; https://doi.org/10.3390/pharmaceutics10040264
Received: 7 November 2018 / Revised: 28 November 2018 / Accepted: 4 December 2018 / Published: 6 December 2018
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-co-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%.
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Keywords:
analgesic adjuvant; ketamine; cancer pain; drug delivery; poly(lactic-co-glycolic acid) (PLGA); sustained release
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MDPI and ACS Style
Han, F.Y.; Whittaker, A.K.; Howdle, S.M.; Naylor, A.; Shabir-Ahmed, A.; Zhang, C.; Smith, M.T. Formulation of Bioerodible Ketamine Microparticles as an Analgesic Adjuvant Treatment Produced by Supercritical Fluid Polymer Encapsulation. Pharmaceutics 2018, 10, 264.
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