Sendil-Keskin D, Altunay H, Wise D L, Hasirci V
Middle East Technical University, Department of Biological Sciences and Biotechnology, Biotechnology Research Unit, 06531 Ankara, Turkey.
J Biomater Sci Polym Ed. 2003;14(6):497-514. doi: 10.1163/15685620360674218.
Pain is the most common and feared symptom for patients, especially those with cancer. Treatment of chronic pain with conventional ways of medication usually fails with increasing severity of the pain. New approaches enabling the prolonged provision of pain relievers are required. We designed a controlled release system of pain relievers, mainly for opioids (morphine, M, codeine, C, and hydromorphone, HM), and a local anesthetic (bupivacaine, BP) in the form of poly(L-lactide-co-glycolide) (PLGA) rods. The efficacy of these rods implanted alone or in combination in relieving chronic pain in rats caused by the ligation of the sciatic nerve of their right hind limbs was studied. The two most common tests for measuring analgesia, i.e. tail-flick tests, that show analgesia at sites other than the site of injury, were used to study the degree of systemic distribution of the drugs and paw-withdrawal tests were used to study the analgesia at the site of injury. Alleviation of this chronic and severe neuropathic pain could be obtained for about 3-4 days when rods for two drugs, 'dual drug' (analgesic-anesthetic), were used. This duration is decreased by half (2 days) with the single-drug rods. Also the dual-drug rods, though at half the dose of each single drug application, enhanced the degree of analgesia of the first day. These in vivo results are also consistent with the previous in vitro results as in the case with codeine which had a higher first-day analgesia than morphine, despite a lower potency due to the faster in vitro release rate. Similarly, slower release of hydromorphone from PLGA (85:15) rods resulted in less systemic analgesia than the more rapidly eroding PLGA (50:50) rods of the same drug.
疼痛是患者，尤其是癌症患者最常见且恐惧的症状。用传统药物治疗慢性疼痛通常会随着疼痛加剧而失效。因此需要新的方法来实现止痛药物的长效供应。我们设计了一种以聚（L-丙交酯-共-乙交酯）（PLGA）棒形式存在的止痛药物控释系统，主要用于阿片类药物（吗啡、M、可待因、C和氢吗啡酮、HM）以及一种局部麻醉剂（布比卡因、BP）。研究了单独植入或联合植入这些棒在缓解大鼠右后肢坐骨神经结扎所致慢性疼痛方面的效果。采用两种最常见的镇痛测量试验，即甩尾试验（该试验可显示损伤部位以外部位的镇痛效果）来研究药物的全身分布程度，采用足趾退缩试验来研究损伤部位的镇痛效果。当使用两种药物的棒，即“双药”（镇痛-麻醉）棒时，这种慢性重度神经性疼痛可缓解约3 - 4天。单药棒的缓解时长减半（2天）。而且双药棒虽然每种单药的剂量减半，但在第一天增强了镇痛程度。这些体内实验结果也与之前的体外实验结果一致，例如可待因的情况，尽管其效力因体外释放速度较快而较低，但第一天的镇痛效果比吗啡更高。同样，氢吗啡酮从PLGA（85:15）棒中的释放较慢，导致其全身镇痛效果比相同药物的侵蚀速度更快的PLGA（50:50）棒更低。
