Controlled release of etoricoxib from poly(ester urea) films for post-operative pain management
| Autor: | Alexandra K. Abel, Andre Hermans, Nathan Z. Dreger, Natasha C. Brigham, Rebecca Nofsinger, Xin Luo, Ru-Rong Ji, Tiffany P. Gustafson, Matthew L. Becker, Seth P. Forster |
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| Rok vydání: | 2020 |
| Předmět: |
Pyridines
Pharmaceutical Science 02 engineering and technology Pharmacology 03 medical and health sciences Etoricoxib Mice Pharmacokinetics Double-Blind Method In vivo Medicine Distribution (pharmacology) Animals Humans Urea Sulfones 030304 developmental biology 0303 health sciences Pain Postoperative Cyclooxygenase 2 Inhibitors business.industry Esters 021001 nanoscience & nanotechnology Controlled release Rats Opioid Delayed-Action Preparations Neuropathic pain Drug delivery 0210 nano-technology business medicine.drug |
| Zdroj: | Journal of controlled release : official journal of the Controlled Release Society. 329 |
| ISSN: | 1873-4995 |
| Popis: | Medical prescriptions for the alleviation of post-surgical pain are the most abundant source of opioids in circulation. As a systemic drug delivery source, opioids leave patients at high risk for side effects after being dosed. Given the significant rate of unauthorized use, distribution, addiction, and opioid related deaths, an alternative method of post-surgical analgesia is needed. Herein, we report the use of bio-resorbable poly(ester urea) (PEU) films that controllably deliver a non-opioid COX-2 inhibitor, etoricoxib, in vivo and in vitro as a model system for post-surgical pain control. PEU composition, drug-load, and film thickness were varied to selectively control etoricoxib elution. Elution data were fit to a Higuchi model, and the diffusion constant of etoricoxib was calculated in each of the films. Pharmacokinetic (pK) data from an in vivo rat model showed the local tissue concentration of etoricoxib at the study endpoint to be up to 23-fold higher in tissue then plasma. In a well-established mouse model of diabetic neuropathic pain in vivo film implantation showed effective relief of pain for more than 4 days post-implantation and efficacious local etoricoxib delivery. Overall, implementation of local drug delivery systems such as this could reduce the need for opioid prescriptions associated with current pain management strategies. |
| Databáze: | OpenAIRE |
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