A single dose of liposome-encapsulated oxymorphone or morphine provides long-term analgesia in an animal model of neuropathic pain.
An extended-release formulation of oxymorphone was produced by encapsulation into liposomes, using a novel technique. Liposome-encapsulated morphine was produced, using a standard technique These preparations were tested in an animal model of neuropathic pain. Male Sprague-Dawley rats (approx. 300 g) were allotted to control (non-loaded liposomes) and treatment (liposome-encapsulated oxymorphone or morphine) groups. Drugs were administered subcutaneously to all rats immediately prior to sciatic nerve ligation. Thermal withdrawal latencies were measured at baseline and daily for seven days after sciatic nerve ligation. A second experiment involved subcutaneous administration of non-loaded liposomes, morphine, or oxymorphone to rats that did not undergo sciatic nerve ligation. Thermal withdrawal latencies in sciatic nerve-ligated rats given non-loaded liposomes decreased significantly by day four, with maximal decrease at day seven after surgery, indicating development of full hyperalgesia. In contrast, ligated rats given liposome-encapsulated morphine or liposome-encapsulated oxymorphone had no decrease in thermal withdrawal latency by day four, indicating that these long-acting preparations prevented development of hyperalgesia after a single injection. This treatment effect persisted to day seven. Non-ligated rats treated with vehicle or liposome-encapsulated morphine had no change in thermal withdrawal latencies. Non-ligated rats treated with liposome-encapsulated oxymorphone had a small, but significant increase in thermal withdrawal latency from day four through day seven. One subcutaneous injection of liposome-encapsulated oxymorphone or morphine was effective in preventing hyperalgesia in this pain model for up to seven days. These results suggest that liposome-encapsulation of oxymorphone offers a novel, convenient, and effective means to provide long-term analgesia.
Smith
Lesley J
LJ
Department of Surgical Sciences, School of Veterinary, University of Wisconsin, 2015 Linden Drive, Madison, Wisconsin 53706, USA.
Krugner-Higby
Lisa
L
Clark
Melanee
M
Wendland
Allyson
A
Heath
Timothy D
TD
D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000827:Animal Welfare; D000818:Animals; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000627:therapeutic use; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004337:Drug Carriers; D006930:Hyperalgesia / Q000503:physiopathology / Q000517:prevention & control*; D007279:Injections, Subcutaneous; D008081:Liposomes; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D010111:Oxymorphone / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries / Q000503:physiopathology; D020426:Sciatic Neuropathy / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology
D000701:Analgesics, Opioid; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D008081:Liposomes; D009020:Morphine; D010111:Oxymorphone