Department of Pharmaceutics and Pharmaceutical Chemistry, University of Utah, Salt Lake City, UT, 84112-5820, USA,
Drug Deliv Transl Res. 2013 Dec;3(6):518-30. doi: 10.1007/s13346-013-0155-x.
Despite clinical, material, and pharmaceutical advances, infection remains a major obstacle in total joint revision surgery. Successful solutions must extend beyond bulk biomaterial and device modifications, integrating locally delivered pharmaceuticals and physiological cues at the implant site, or within large bone defects with prominent avascular spaces. One approach involves coating clinically familiar allograft bone with an antibiotic-releasing rate-controlling polymer membrane for use as a matrix for local drug release in bone. The kinetics of drug release from this system can be tailored via alterations in the substrate or the polymeric coating. Drug-loaded polycaprolactone coating releases bioactive tobramycin from both cadaveric-sourced cancellous allograft fragments and synthetic hybrid coralline ceramic bone graft fragments with similar kinetics over a clinically relevant 6-week timeframe. However, micron-sized allograft particulate provides extended bioactive tobramycin release. Addition of porogen polyethylene glycol to the polymer coating formulation changes tobramycin release kinetics without significant impact on released antibiotic bioactivity. Incorporation of oil-microencapsulated tobramycin into the polymer coating did not significantly modify tobramycin release kinetics. In addition to releasing inhibitory concentrations of tobramycin, antibiotic-loaded allograft bone provides recognized beneficial osteoconductive potential, attractive for decreasing orthopedic surgical infections with improved filling of dead space and new bone formation.
尽管在临床、材料和药物方面取得了进展，但感染仍然是全关节翻修手术的主要障碍。成功的解决方案必须超越大块生物材料和器械的改进，整合局部输送的药物和生理信号，或在有明显无血管空间的大骨缺损处。一种方法是将具有抗生素释放率控制聚合物膜的临床熟悉同种异体骨进行涂层，用作骨内局部药物释放的基质。通过改变基质或聚合涂层，可以调整该系统的药物释放动力学。载药聚己内酯涂层可从尸体来源的松质同种异体骨碎片和合成混合珊瑚陶瓷骨移植物碎片中释放出具有生物活性的妥布霉素，在临床相关的 6 周时间内，其释放动力学相似。然而，微米级同种异体颗粒提供了延长的具有生物活性的妥布霉素释放。在聚合物涂层配方中添加致孔剂聚乙二醇会改变妥布霉素的释放动力学，而不会对释放的抗生素生物活性产生显著影响。将油包载妥布霉素微胶囊化到聚合物涂层中不会显著改变妥布霉素的释放动力学。除了释放具有抑制浓度的妥布霉素外，负载抗生素的同种异体骨还提供了公认的有益成骨潜力，有助于减少骨科手术感染，通过填充死腔和新骨形成来改善填充效果。
