Opioid analgesics such as morphine are widely used to treat severe acute and chronic pain. However, morphine has a short half-life in plasma, necessitating frequent dosing (every 2-4 hours) to maintain its analgesic effect. Repeated administration is not desired as it may lead to poor compliance (e.g., missing doses or administering doses too early). To overcome these issues, the Uhrich lab has developed a biodegradable, polymeric version of morphine (PolyMorphine) for extended analgesia. The chemical incorporation of morphine into a poly(anhydride ester) backbone allows for the near zero-order drug release upon hydrolytic degradation. Furthermore, the morphine in the polymer cannot be separated by physical means (i.e., crushing the polymer), potentially reducing the possibility of an overdose, either accidental or as the result of abuse. In vivo studies using mice proved that PolyMorphine provides analgesia for 3 days, 20 times the analgesic window of free morphine. These results demonstrate, for the first time, a systemically administered prodrug that affords such a long analgesic effect.
Patents related to this research:
- Uhrich, KE “Therapeutic polyesters and polyamides”; US PN 8,221,790 (issued July 17, 2012)
- Uhrich, KE “Therapeutics Compositions and Methods”; US PN 8,088,405 (issued January 3, 2012)
- Uhrich, KE “Polyanhydrides with Therapeutically Useful Degradation Products”; US PN 8,017,714 (issued September 13, 2011)
Rosario-Meléndez R, Harris CL, Delgado-Rivera R, Yu L, Uhrich KE.; "PolyMorphine: an innovative biodegradable polymer drug for extended pain relief."; J Control Release. 2012 Sep 28;162(3):538-44. doi: 10.1016/j.jconrel.2012.07.033
Nick Stebbins, Graduate Student and Roselin Rosario-Meléndez, PhD