Smith Lesley J, Krugner-Higby Lisa, Clark Melanee, Wendland Allyson, Heath Timothy D
Department of Surgical Sciences, School of Veterinary, University of Wisconsin, 2015 Linden Drive, Madison, Wisconsin 53706, USA.
Comp Med. 2003 Jun;53(3):280-7.
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.
采用一种新技术，通过将羟考酮包裹于脂质体中制备了一种缓释制剂。使用标准技术制备了脂质体包裹的吗啡。这些制剂在神经性疼痛的动物模型中进行了测试。将雄性斯普拉格-道利大鼠（约300克）分配至对照组（未负载脂质体）和治疗组（脂质体包裹的羟考酮或吗啡）。在坐骨神经结扎前，立即对所有大鼠皮下给药。在基线时以及坐骨神经结扎后七天每天测量热退缩潜伏期。第二个实验涉及对未进行坐骨神经结扎的大鼠皮下给予未负载脂质体、吗啡或羟考酮。给予未负载脂质体的坐骨神经结扎大鼠的热退缩潜伏期在第四天显著降低，在术后第七天降至最低，表明出现了完全性痛觉过敏。相比之下，给予脂质体包裹的吗啡或脂质体包裹的羟考酮的结扎大鼠在第四天热退缩潜伏期没有降低，表明这些长效制剂单次注射后可预防痛觉过敏的发生。这种治疗效果持续到第七天。用赋形剂或脂质体包裹的吗啡治疗的未结扎大鼠的热退缩潜伏期没有变化。用脂质体包裹的羟考酮治疗的未结扎大鼠在第四天至第七天热退缩潜伏期有小幅但显著的增加。在该疼痛模型中，单次皮下注射脂质体包裹的羟考酮或吗啡可有效预防长达七天的痛觉过敏。这些结果表明，脂质体包裹的羟考酮提供了一种新颖、便捷且有效的长期镇痛方法。
