Development of Triamcinolone Acetonide-Loaded Nanoparticles for Inflammatory Knee Arthritis Treatment

Shu-Jyuan Yang,1,* Tzu-Hao Tseng,2,* Po-Ju Ting,1 Yao-Chang Lo,3 Tai-Horng Young,1 Chih-Hao Chang21Department of Biomedical Engineering, College of Medicine and College of Engineering, National Taiwan University, Taipei, Taiwan; 2Department of Orthopedics, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; 3Department of Orthopedic Surgery, National Taiwan University Hospital, Taipei, Taiwan*These authors contributed equally to this workCorrespondence: Chih-Hao Chang, Email mike920@gmail.comIntroduction: Intra-articular corticosteroid injections (IACIs) provide an alternative treatment for inflammatory arthritis. Nevertheless, IACIs are limited by adverse effects, including injection-related pain, corticosteroid-induced chondrocyte toxicity, and progressive cartilage degeneration following prolonged use.Methods: In this study, human serum albumin (HSA) was employed as a biocompatible nanocarrier for the encapsulation of triamcinolone acetonide (TA) to develop TA/HSA nanoparticles (TA/HSA NPs). The physicochemical characteristics and drug-release profile of the TA/HSA NPs were characterized. The in vitro cytocompatibility was evaluated in Hs68 fibroblasts, chondrocytes, and MG-63 osteoblast-like cells. The therapeutic efficacy of TA/HSA NPs was further evaluated in an inflammatory knee arthritis model following intra-articular administration.Results: This system could significantly decrease the direct cytotoxicity of TA and achieve rapid and sustained release of TA in the joint cavity by reducing the crystallization properties of TA. Due to the sustained release of TA from TA/HSA NPs, the intra-articular injection of TA/HSA NPs could reduce inflammation-induced knee swelling, extend its anti-inflammatory effects, and thereby protect against cartilage erosion and condyle damage.Conclusion: TA/HSA NPs represent a promising intra-articular drug delivery strategy for inflammatory arthritis. The formulation reduced the cytotoxicity of TA and provided sustained drug release in vitro, while demonstrating enhanced anti-inflammatory and cartilage-protective effects in an MIA-induced arthritis model.Keywords: inflammatory arthritis, triamcinolone acetonide, human serum albumin, nanomedicine, anti-inflammatory