Novel prolonged-release polymeric microparticles for relief of intractable cancer-related pain (2016–2018)
For the 10-30% of patients with advanced cancer who experience unremitting severe pain despite administration of escalating doses of clinically available analgesics by conventional oral or parenteral routes, more invasive dosing routes may be warranted. These include chronic implantation of programmable pumps, accessible reservoir systems, and tunneled, exteriorized catheters. Intra-spinal delivery systems enable logarithmic scale reductions in medication dosing relative to systemic routes of administration. Pain medications that have been given spinally include strong opioid analgesics (e.g. morphine and hydromorphone), local anaesthetics (e.g. lignocaine), alpha2-agonists (e.g. clonidine) and ziconotide. Intra-spinal delivery systems enable logarithmic scale reductions in medication dosing relative to systemic dosing routes. Due to the close proximity of the administered analgesic/adjuvant agents to their target receptors and ion channels, analgesia has a longer duration and systemic side-effects are reduced. However, use of implanted devices is associated with a range of catheter-related problems that occur in up to 25% of patients, including kinking, obstruction, disconnection, and granuloma formation at the catheter tip with prolonged, high-rate infusion. Hence, we will address these issues by developing biodegradable prolonged-release polymer formulations of pain-relieving drugs for administration by the intrathecal route in close proximity to their target receptors or ion channels in the spinal cord, as a means to produce prolonged periods of analgesia with markedly reduced systemic side-effects.