Epidural administration of liposome-encapsulated hydromorphone provides extended analgesia in a rodent model of stifle arthritis.

Liposome encapsulation of opioids by using an ammonium-sulfate-gradient loading technique significantly slows the release time of the drug. This study evaluated the duration of analgesia in a rodent model of monoarthritis after epidural administration of liposome-encapsulated hydromorphone (LE-hydromorphone; prepared by ammonium-sulfate-gradient loading) compared with standard hydromorphone and a negative control of blank liposomes. Analgesia was assessed by changes in thermal withdrawal latency, relative weight-bearing, and subjective behavioral scoring. Analgesia in arthritic rats was short-lived after epidural hydromorphone; increases in pain threshold were observed only at 2 h after administration. In contrast, thermal pain thresholds after epidural LE-hydromorphone were increased for as long as 72 h, and subjective lameness scores were lower for as long as 96 h after epidural administration. Injection of LE-hydromorphone epidurally was associated with various mild changes in CNS behavior, and 2 rats succumbed to respiratory depression and death. In conclusion, LE-hydromorphone prolonged the duration of epidural analgesia compared with the standard formulation of hydromorphone, but CNS side effects warrant careful administration of this LE-hydromorphone in future studies.