Tailored sequential drug release from bilayered calcium sulfate composites.
Tailored sequential drug release from bilayered calcium sulfate composites.
复制标题
从双层硫酸钙复合材料中定制的连续药物释放。
DOI：
10.1016/j.msec.2014.06.044
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Puleo,DavidA
中科院分区：
文献类型：
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作者：
Orellana,BryanR;Puleo,DavidA
目前治疗受感染骨缺损的标准，如由牙周病引起的骨缺损，需要多个耗时的步骤，通常需要多个程序来对抗感染和恢复失去的组织。从人工骨移植替代物中释放抗生素和成骨剂可以简化治疗，减少多次手术的需要，从而缩短恢复时间。可定制的双层硫酸钙（CS）骨移植替代物具有顺序释放多种治疗剂的能力。制备具有壳和核几何形状的双层复合样品，在壳中嵌入不同数量（1或10 wt.%）的甲硝唑负载聚乳酸-羟基乙酸（PLGA）颗粒，并将辛伐他汀直接加载到壳、核或两者中。微计算机断层扫描显示了整体层状几何结构以及壳内PLGA的均匀分布。溶解研究表明，PLGA颗粒的数量（即1 wt.% vs. 10 wt.%）对侵蚀速率（3% vs. 3.4%/d）有很小但显著的影响。力学测试确定，引入分层几何结构对抗压强度有显著影响，平均降低35%，但性能与下颌小梁骨相当。辛伐他汀直接装入CS的缓释实验表明，改变壳核体积比决定了药物从每层释放的持续时间。将甲硝唑和辛伐他汀分别装入壳中或单独装入层中，实现了甲硝唑和辛伐他汀的顺序释放。通过引入一种可调节的、能够释放多种药物的分层几何结构，基于cs的骨移植替代品可以被定制，以帮助简化在感染缺陷中再生组织所需的多个步骤。
The current standard for treating infected bony defects, such as those caused by periodontal disease, requires multiple time-consuming steps and often multiple procedures to fight the infection and recover lost tissue. Releasing an antibiotic followed by an osteogenic agent from a synthetic bone graft substitute could allow for a streamlined treatment, reducing the need for multiple surgeries and thereby shortening recovery time. Tailorable bilayered calcium sulfate (CS) bone graft substitutes were developed with the ability to sequentially release multiple therapeutic agents. Bilayered composite samples having a shell and core geometry were fabricated with varying amounts (1 or 10 wt.%) of metronidazole-loaded poly(lactic-co-glycolic acid) (PLGA) particles embedded in the shell and simvastatin directly loaded into either the shell, core, or both. Microcomputed tomography showed the overall layered geometry as well as the uniform distribution of PLGA within the shells. Dissolution studies demonstrated that the amount of PLGA particles (i.e., 1 vs. 10 wt.%) had a small but significant effect on the erosion rate (3% vs. 3.4%/d). Mechanical testing determined that introducing a layered geometry had a significant effect on the compressive strength, with an average reduction of 35%, but properties were comparable to those of mandibular trabecular bone. Sustained release of simvastatin directly loaded into CS demonstrated that changing the shell to core volume ratio dictates the duration of drug release from each layer. When loaded together in the shell or in separate layers, sequential release of metronidazole and simvastatin was achieved. By introducing a tunable, layered geometry capable of releasing multiple drugs, CS-based bone graft substitutes could be tailored in order to help streamline the multiple steps needed to regenerate tissue in infected defects.