Hulse G K, Stalenberg V, McCallum D, Smit W, O'neil G, Morris N, Tait R J
Unit for Research and Education in Drugs and Alcohol, School of Psychiatry and Clinical Neurosciences, The University of Western Australia, Crawley, and Department of Pathology, Royal Perth Hospital, WA, Australia.
J Control Release. 2005 Nov 2;108(1):43-55. doi: 10.1016/j.jconrel.2005.08.001. Epub 2005 Sep 9.
In order to assess the histological tissue changes over time around the site of implant, tissue biopsies were taken at 1 to 38 months post-implant from 54 (34 male) consenting human subjects who had received the Australian subcutaneous naltrexone-poly(DL-lactide) implant for heroin dependence. The implant consists of multiple tablets containing compressed naltrexone-poly[trans-3,6-dimethyl-1,4-dioxane-2,5-dione] (DL-lactide) loaded microspheres. Assessment of tissue samples by pathologists showed an early phase (up to 12 months post-implant) of inflammation, foreign body reaction, and fibrosis. This subsided gradually over the next 12 months until tissue returned to normal by 25+ months. Sufficient evidence was not available to conclude that the poly(DL-lactide) implant matrix was totally biodegradable within the study period. While implant material was not identified in most of the latter biopsies, its presence was noted in one biopsy at 26 months post-implant. Nevertheless the study results did demonstrate the implant's biocompatibility by the lack of inflammation, foreign body reaction, and fibrosis detected by 25+ months. It seems highly probable that surgical technique rather than the implant itself was associated with the additional finding of fat necrosis. Moderate fat necrosis was observed as a common feature of biopsies carried out during the first 6 months following implant. It subsided to mild levels over the next 18 months, and was notably absent by 25+ months. The results of the study indicated that the Australian naltrexone-poly(DL-lactide) implant is well tolerated and may have a role for use in the management of medical conditions such as heroin dependence.
为了评估植入部位周围组织随时间的组织学变化，对54名（34名男性）接受澳大利亚皮下纳曲酮-聚（DL-丙交酯）植入物治疗海洛因依赖的受试者在植入后1至38个月进行了组织活检。该植入物由多个片剂组成，片剂中含有压缩的纳曲酮-聚[反式-3,6-二甲基-1,4-二恶烷-2,5-二酮]（DL-丙交酯）负载微球。病理学家对组织样本的评估显示，在植入后的早期阶段（长达12个月）出现了炎症、异物反应和纤维化。在接下来的12个月中，这种情况逐渐消退，直到25个月以上组织恢复正常。没有足够的证据得出聚（DL-丙交酯）植入物基质在研究期间完全可生物降解的结论。虽然在大多数后期活检中未发现植入材料，但在植入后26个月的一次活检中注意到了其存在。然而，研究结果确实通过在25个月以上未检测到炎症、异物反应和纤维化证明了植入物的生物相容性。似乎很有可能是手术技术而非植入物本身与脂肪坏死的额外发现有关。在植入后的前6个月进行的活检中，中度脂肪坏死是常见特征。在接下来的18个月中，它消退到轻度水平，在25个月以上时明显不存在。研究结果表明，澳大利亚的纳曲酮-聚（DL-丙交酯）植入物耐受性良好，可能在治疗海洛因依赖等医疗状况中发挥作用。
