Development of hyaluronic acid hydrogel containing prednisolone‐encapsulated nonphospholipid liposomes for the treatment of rheumatoid arthritis

Abstract

AbstractRheumatoid arthritis (RA) requires therapeutic approaches that alleviate symptoms and inhibit the progression of joint damage. Glucocorticoids (GCs) have been a cornerstone of RA treatment, yet their use is often limited by side effects. Recent advancements suggest that liposome‐based delivery systems can improve GC biodistribution, minimizing toxicity. This study introduces an innovative tool for RA treatment using prednisone‐encapsulated nonphospholipid liposomes (NPLs) in combination with a hyaluronic acid (HA) hydrogel. Our methodology involved incorporating prednisone (PR) with palmitic acid and cholesterol to formulate stable NPLs using a thin‐film hydration technique. The synthesized PR‐NPLs, characterized by a mean size of 150 nm, demonstrated uniform distribution and higher drug encapsulation in comparison with conventional phospholipid liposomes. In vitro assays revealed that PR‐NPL markedly reduced inflammatory responses in macrophages. Additionally, we successfully incorporated PR‐NPL into an HA hydrogel, employing a photoinitiated cross‐linking process. This novel composite offered modulable PR release, governed by the degree of hydrogel cross‐linking. The developed system presents a promising advancement in RA management, especially suited for intraarticular injections. It potentially enables targeted, controlled drug release with a reduced risk of side effects, signifying a significant improvement over existing RA therapies.