Formulation of Bioerodible Ketamine Microparticles as an Analgesic Adjuvant Treatment Produced by Supercritical Fluid Polymer Encapsulation
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 pr...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2018-12-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/10/4/264 |
| _version_ | 1811304108901007360 |
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| author | Felicity Y. Han Andrew K. Whittaker Steven M. Howdle Andrew Naylor Anjumn Shabir-Ahmed Cheng Zhang Maree T. Smith |
| author_facet | Felicity Y. Han Andrew K. Whittaker Steven M. Howdle Andrew Naylor Anjumn Shabir-Ahmed Cheng Zhang Maree T. Smith |
| author_sort | Felicity Y. Han |
| collection | DOAJ |
| description | 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-<i>co</i>-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%. |
| first_indexed | 2024-04-13T08:01:30Z |
| format | Article |
| id | doaj.art-642895c52bf94bb4b194afe7b11d3364 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-13T08:01:30Z |
| publishDate | 2018-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-642895c52bf94bb4b194afe7b11d33642022-12-22T02:55:17ZengMDPI AGPharmaceutics1999-49232018-12-0110426410.3390/pharmaceutics10040264pharmaceutics10040264Formulation of Bioerodible Ketamine Microparticles as an Analgesic Adjuvant Treatment Produced by Supercritical Fluid Polymer EncapsulationFelicity Y. Han0Andrew K. Whittaker1Steven M. Howdle2Andrew Naylor3Anjumn Shabir-Ahmed4Cheng Zhang5Maree T. Smith6School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane QLD 4072, AustraliaAustralian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane QLD 4072, AustraliaSchool of Chemistry, University of Nottingham, Nottingham NG7 2RD, UKUpperton Limited, Biocity Nottingham, Nottingham NG7 2TN, UKCritical Pharmaceuticals Ltd., BioCity Nottingham, Nottingham NG1 1GF, UKAustralian Institute for Bioengineering and Nanotechnology, The University of Queensland, Brisbane QLD 4072, AustraliaSchool of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Brisbane QLD 4072, AustraliaPain 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-<i>co</i>-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%.https://www.mdpi.com/1999-4923/10/4/264analgesic adjuvantketaminecancer paindrug deliverypoly(lactic-<i>co</i>-glycolic acid) (PLGA)sustained release |
| spellingShingle | Felicity Y. Han Andrew K. Whittaker Steven M. Howdle Andrew Naylor Anjumn Shabir-Ahmed Cheng Zhang Maree T. Smith Formulation of Bioerodible Ketamine Microparticles as an Analgesic Adjuvant Treatment Produced by Supercritical Fluid Polymer Encapsulation Pharmaceutics analgesic adjuvant ketamine cancer pain drug delivery poly(lactic-<i>co</i>-glycolic acid) (PLGA) sustained release |
| title | Formulation of Bioerodible Ketamine Microparticles as an Analgesic Adjuvant Treatment Produced by Supercritical Fluid Polymer Encapsulation |
| title_full | Formulation of Bioerodible Ketamine Microparticles as an Analgesic Adjuvant Treatment Produced by Supercritical Fluid Polymer Encapsulation |
| title_fullStr | Formulation of Bioerodible Ketamine Microparticles as an Analgesic Adjuvant Treatment Produced by Supercritical Fluid Polymer Encapsulation |
| title_full_unstemmed | Formulation of Bioerodible Ketamine Microparticles as an Analgesic Adjuvant Treatment Produced by Supercritical Fluid Polymer Encapsulation |
| title_short | Formulation of Bioerodible Ketamine Microparticles as an Analgesic Adjuvant Treatment Produced by Supercritical Fluid Polymer Encapsulation |
| title_sort | formulation of bioerodible ketamine microparticles as an analgesic adjuvant treatment produced by supercritical fluid polymer encapsulation |
| topic | analgesic adjuvant ketamine cancer pain drug delivery poly(lactic-<i>co</i>-glycolic acid) (PLGA) sustained release |
| url | https://www.mdpi.com/1999-4923/10/4/264 |
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