Villamagna Ian J, McRae Danielle M, Borecki Aneta, Mei Xueli, Lagugné-Labarthet François, Beier Frank, Gillies Elizabeth R
School of Biomedical Engineering, The University of Western Ontario, London, ON N6A 5B9, Canada.
Bone and Joint Institute, The University of Western Ontario, London, ON N6A 5B9, Canada.
Polymers (Basel). 2020 Mar 26;12(4):736. doi: 10.3390/polym12040736.
Osteoarthritis (OA) is a debilitating joint disorder affecting more than 240 million people. There is no disease modifying therapeutic, and drugs that are used to alleviate OA symptoms result in side effects. Recent research indicates that inhibition of peroxisome proliferator-activated receptor δ (PPARδ) in cartilage may attenuate the development or progression of OA. PPARδ antagonists such as GSK3787 exist, but would benefit from delivery to joints to avoid side effects. Described here is the loading of GSK3787 into poly(ester amide) (PEA) particles. The particles contained 8 wt.% drug and had mean diameters of about 600 nm. Differential scanning calorimetry indicated the drug was in crystalline domains in the particles. Atomic force microscopy was used to measure the Young's moduli of individual particles as 2.8 MPa. In vitro drug release studies showed 11% GSK3787 was released over 30 days. Studies in immature murine articular cartilage (IMAC) cells indicated low toxicity from the drug, empty particles, and drug-loaded particles and that the particles were not taken up by the cells. Ex vivo studies on murine joints showed that the particles could be injected into the joint space and resided there for at least 7 days. Overall, these results indicate that GSK3787-loaded PEA particles warrant further investigation as a delivery system for potential OA therapy.
骨关节炎（OA）是一种使人衰弱的关节疾病，影响着超过2.4亿人。目前尚无改善病情的治疗方法，用于缓解OA症状的药物会产生副作用。最近的研究表明，抑制软骨中的过氧化物酶体增殖物激活受体δ（PPARδ）可能会减缓OA的发展或进程。虽然存在如GSK3787这样的PPARδ拮抗剂，但将其递送至关节以避免副作用会更有益处。本文描述了将GSK3787负载到聚（酯酰胺）（PEA）颗粒中的过程。这些颗粒含有8 wt.%的药物，平均直径约为600 nm。差示扫描量热法表明药物存在于颗粒的结晶区域中。原子力显微镜用于测量单个颗粒的杨氏模量为2.8 MPa。体外药物释放研究表明，在30天内有11%的GSK3787被释放。对未成熟小鼠关节软骨（IMAC）细胞的研究表明，药物、空颗粒和载药颗粒的毒性较低，且细胞不会摄取这些颗粒。对小鼠关节的离体研究表明，这些颗粒可以注射到关节腔中并在那里停留至少7天。总体而言，这些结果表明，负载GSK3787的PEA颗粒作为潜在OA治疗的递送系统值得进一步研究。
