Jayaram Rohith, O'Donnell Patrick W, Puleo David A
F. Joseph Halcomb III, M.D. Department of Biomedical Engineering, University of Kentucky, Lexington, KY 40506, USA.
Department of Orthopaedic Surgery and Markey Cancer Center, University of Kentucky, Lexington, KY 40536, USA.
Mater Sci Eng C Mater Biol Appl. 2021 Jan;118:111395. doi: 10.1016/j.msec.2020.111395. Epub 2020 Aug 22.
Bone pain is the leading cause of morbidity in patients with metastatic cancer. Systemic administration of zoledronic acid (ZA) decreases skeletally-related events in bone cancer patients but is associated with major side effects. This project investigated two biomaterials, poly(methyl methacrylate) (PMMA) bone cement and poly(lactic-co-glycolic acid) (PLGA), for local ZA delivery. Compressive properties of PMMA samples were tested with increased drug loading, and in vitro ZA release profiles from PMMA cylinders and PLGA films were measured over 8 weeks. The activity of ZA eluted from both materials was evaluated on the RAW 264.7 macrophage cell line. PMMA samples released up to only 17% of incorporated drug, whereas PLGA films released over 95%. A burst profile was observed for PMMA, while ZA release from PLGA exhibited a typical triphasic profile. Drug bioactivity remained above 50% for both materials. Local ZA delivery from these materials may be useful in the treatment of metastatic bone cancer.
骨痛是转移性癌症患者发病的主要原因。唑来膦酸（ZA）的全身给药可减少骨癌患者的骨相关事件，但会伴有严重的副作用。本项目研究了两种生物材料，聚甲基丙烯酸甲酯（PMMA）骨水泥和聚乳酸-羟基乙酸共聚物（PLGA），用于局部ZA递送。测试了药物负载量增加时PMMA样品的压缩性能，并在8周内测量了PMMA圆柱体和PLGA薄膜的体外ZA释放曲线。从两种材料中洗脱的ZA活性在RAW 264.7巨噬细胞系上进行了评估。PMMA样品仅释放了高达17%的掺入药物，而PLGA薄膜释放了超过95%。观察到PMMA有一个突释曲线，而PLGA的ZA释放呈现典型的三相曲线。两种材料的药物生物活性均保持在50%以上。这些材料的局部ZA递送可能对转移性骨癌的治疗有用。
