Therapeutic effects of curcumin liposomes and nanocrystals on inflammatory osteolysis: In vitro and in vivo comparative study

作者：Shan Huang, Dongdong Xu, Li Zhang, Hao Liang, Yujie Jia, Xianlong Zhang, Tao Cheng, Jian Chen · 发表于：Pharmacological Research · 年份：2023 · DOI：10.1016/j.phrs.2023.106778 · 被引用次数：37 · 研究领域：Orthopaedic implants and arthroplasty、Orthopedic Infections and Treatments、Bone and Joint Diseases

Curcumin could inhibit periprosthetic osteolysis induced by wear debris and adherent endotoxin, which commonly cause prosthesis loosening and negatively influence the long-term survival of joint arthroplasty. However, its limited water solubility and poor stability pose challenges for its further clinical application. To address these issues, we developed curcumin liposomes for intraarticular injection, as liposomes possess good lubricant capacity and pharmacological synergy with curcumin. Additionally, a nanocrystal dosage form was prepared to enable comparison with the liposomes based on their ability to disperse curcumin effectively. A microfluidic method was used for its controllability, repeatability, and scalability. The Box-Behnken Design was employed to screen the formulations and flow parameters, while computational fluid dynamics was used to simulate the mixing process and predict the formation of liposomes. The optimized curcumin liposomes (Cur-LPs) had a size of 132.9 nm and an encapsulation efficiency of 97.1%, whereas the curcumin nanocrystals (Cur-NCs) had a size of 172.3 nm. Both Cur-LPs and Cur-NCs inhibited LPS-induced pro-inflammatory polarization of macrophages and reduced the expression and secretion of inflammatory factors. The mouse air pouch model further demonstrated that both dosage forms attenuated inflammatory cell infiltration and inflammatory fibrosis in subcutaneous tissues. Interestingly, the anti-inflammatory effect of Cur-LPs was more potent ...