Abstract
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%.
Highlights
Unrelenting severe cancer-related pain, that complicated by a neuropathic component, is difficult to alleviate by escalating doses of strong opioid analgesics such as morphine given alone or in combination with adjuvant analgesic agents by conventional systemic dosing routes [1]
There is some evidence that, in the postoperative setting, adding ketamine to an opioid in patient-controlled analgesia has a beneficial effect on pain relief, is morphine-sparing, and produces less postoperative nausea and vomiting compared with equi-effective opioid analgesic administration alone [6,7]
These findings suggest that i.t. co-administration of a strong opioid analgesic with low-dose ketamine in close proximity to their target receptors/ion channels in the spinal cord may produce satisfactory analgesia
Summary
Unrelenting severe cancer-related pain, that complicated by a neuropathic (nerve damage) component, is difficult to alleviate by escalating doses of strong opioid analgesics such as morphine given alone or in combination with adjuvant analgesic agents by conventional systemic dosing routes [1]. There is some evidence that, in the postoperative setting, adding ketamine to an opioid in patient-controlled analgesia has a beneficial effect on pain relief, is morphine-sparing, and produces less postoperative nausea and vomiting compared with equi-effective opioid analgesic administration alone [6,7]. Co-injection of ketamine with a strong opioid analgesic attenuated the development of analgesic tolerance and enhanced pain relief [10]. Together, these findings suggest that i.t. co-administration of a strong opioid analgesic with low-dose ketamine in close proximity to their target receptors/ion channels in the spinal cord may produce satisfactory analgesia
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