School of Biomedical Engineering, The University of Western Ontario, London, Ontario N6A 5B9, Canada.
Bone and Joint Institute, The University of Western Ontario, London, Ontario N6A 5B9, Canada.
J Biomed Mater Res A. 2019 Jun;107(6):1235-1243. doi: 10.1002/jbm.a.36632. Epub 2019 Feb 22.
Many potential pharmacological treatments for osteoarthritis can result in undesirable side effects due to the systemic administration of drugs, making the direct delivery of drugs to joints an attractive alternative. Poly(ester amide)s (PEAs) have been shown to exhibit promising properties for the development of particle-based intra-articular delivery vehicles. However, a limited range of PEA structures has been investigated. In this study, we prepared and characterized the properties of two different PEA particles composed of l-phenylalanine, sebacic acid, and either 1,4-butanediol or 1,8-octanediol (PBSe and POSe, respectively). The anti-inflammatory drug celecoxib (CXB) was encapsulated into the particles. Despite minor structural differences, PBSe and POSe exhibited different thermal and mechanical properties, and encapsulation of CXB influenced these properties. PBSe-CXB particles provided a slower release of drug in vitro relative to POSe-CXB. Toxicity studies showed that particles without drug exhibited low toxicity to ATDC5 and C2C12 cells, while the PBSe-CXB particles exhibited concentration-dependent toxicity. Host response to the particles was evaluated in an ovine model. No adverse effects were observed following intra-articular injection and it was observed that the particles diffused into the surrounding tissues. This work shows the importance of structural tuning in PEA delivery vehicles and demonstrates their potential for further development. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1235-1243, 2019.
许多潜在的治疗骨关节炎的药物疗法由于药物的全身给药会导致不良的副作用，因此将药物直接递送到关节成为一种有吸引力的替代方法。聚（酯酰胺）（PEA）已被证明在开发基于颗粒的关节内递药载体方面具有有前景的特性。然而，研究的 PEA 结构的范围有限。在本研究中，我们制备并表征了由 l-苯丙氨酸、癸二酸和 1,4-丁二醇或 1,8-辛二醇组成的两种不同 PEA 颗粒（分别为 PBSe 和 POSe）的性质。将抗炎药物塞来昔布（CXB）包封到颗粒中。尽管存在微小的结构差异，但 PBSe 和 POSe 表现出不同的热学和力学性能，并且 CXB 的包封影响了这些性能。与 POSe-CXB 相比，PBSe-CXB 颗粒在体外表现出药物释放更缓慢。毒性研究表明，不含药物的颗粒对 ATDC5 和 C2C12 细胞表现出低毒性，而 PBSe-CXB 颗粒则表现出浓度依赖性毒性。在绵羊模型中评估了颗粒对宿主的反应。关节内注射后没有观察到不良反应，并且观察到颗粒扩散到周围组织中。这项工作表明在 PEA 递药载体中结构调谐的重要性，并证明了它们进一步开发的潜力。© 2019 Wiley Periodicals, Inc. J 生物医学材料研究杂志 A 部分：107A：1235-1243，2019。
