Experimental and Regenerative Neurosciences, School of Animal Biology (M317), The University of Western Australia, 35 Stirling Highway, Crawley, WA 6009, Australia.
J Biomed Mater Res A. 2009 Dec 15;91(4):964-74. doi: 10.1002/jbm.a.32283.
Oral naltrexone is used to treat alcohol and heroin dependence but is associated with poor patient compliance. Sustained-release preparations have been developed to overcome noncompliance. Many sustained-release preparations are composed of polymers combined with naltrexone. Limited data indicate that polymers induce variable levels of tissue reactivity and that naltrexone may increase this effect. A slow-release subcutaneous naltrexone-poly (DL-lactide) implant is currently being trialed to treat heroin dependence in Western Australia. A minority of women fall pregnant and, although tissue reactivity in nonpregnant humans is relatively minor, detailed chronological data during pregnancy are lacking. Histological changes in pregnant rats were assessed; a single active tablet containing poly[trans-3,6-dimethyl-1,4-dioxyane-2,5-dione] (DL-lactide) loaded with 25 mg of naltrexone was implanted subcutaneously, and tissue response was compared with inactive polymer implantation. Rats were timed mated at 13-26 days postimplant. Tissue assessment up to 75 days by a pathologist showed that naltrexone induced chronic inflammatory response in a dose-dependent manner, although still at a low level. Furthermore, for inactive implants, minimal foreign body reaction and fibrosis, together with low-level inflammation, suggested good long-term biocompatibility. We conclude that the Australian naltrexone-poly(DL-lactide) implant is tolerated in pregnant rats, reinforcing its potential role for managing alcohol and heroin dependence in pregnant humans.
口服纳曲酮用于治疗酒精和海洛因依赖，但与患者依从性差有关。为了克服不依从性，已经开发了缓释制剂。许多缓释制剂由与纳曲酮结合的聚合物组成。有限的数据表明，聚合物诱导不同程度的组织反应，而纳曲酮可能会增加这种效果。目前正在西澳大利亚试用一种缓慢释放的皮下纳曲酮-聚（DL-丙交酯）植入物来治疗海洛因依赖。少数女性怀孕，尽管非孕妇的组织反应相对较小，但缺乏怀孕期间的详细时间数据。评估了怀孕大鼠的组织变化；将含有 25 毫克纳曲酮的单个活性片剂植入皮下，该片剂由聚[反式-3,6-二甲基-1,4-二氧杂环己烷-2,5-二酮]（DL-丙交酯）负载，将组织反应与非活性聚合物植入进行比较。大鼠在植入后 13-26 天进行定时交配。组织评估在 75 天内由病理学家进行，结果表明纳曲酮以剂量依赖的方式引起慢性炎症反应，尽管仍处于低水平。此外，对于非活性植入物，最小的异物反应和纤维化，以及低水平的炎症，表明具有良好的长期生物相容性。我们得出结论，澳大利亚的纳曲酮-聚（DL-丙交酯）植入物在怀孕大鼠中耐受良好，这增强了其在管理孕妇酒精和海洛因依赖方面的潜在作用。
