Liposome-based nanocolloids for restoring lubrication and targeted therapy in osteoarthritis.

Osteoarthritis (OA) is a prevalent degenerative joint disease characterized by joint pain, stiffness, and locomotor restriction. With over 600 million affected individuals globally, current surgical interventions often bring high costs and postoperative recovery problems, underscoring the urgent need for minimally invasive therapeutic strategies. Phosphatidylcholines (PCs), critical constituents of the natural lubricating layer on the articular cartilage surface, play a pivotal role in maintaining low-friction joint motion. Liposomes, spherical vesicles composed of phospholipid bilayers, have been extensively explored as drug delivery vehicles due to their structural mimicry of biological membranes and excellent biocompatibility. These properties enable efficient encapsulation and targeted delivery of anti-inflammatory drugs to inflamed joints. Contemporary research emphasizes the development of OA microenvironment-responsive liposomal systems engineered for sustained drug release by intra-articular (IA) injections. By leveraging pathological features of OA (such as elevated protease activity or acidic pH), these systems achieve spatiotemporally controlled drug release, prolonging therapeutic efficacy while minimizing cartilage abrasion. At the same time, functionalizing liposomes with synergistic lubricating biomaterials or cartilage-binding ligands has emerged as a dual-functional strategy. Such modifications enhance liposome adhesion to cartilage, prolong IA retention, and restore boundary lubrication by replenishing depleted phospholipid layers, thereby reducing the coefficient of friction (COF) and alleviating pain. This enables the simultaneous reduction of physical friction (via hydration lubrication) and chemical suppression of inflammation (via targeted drug delivery), together breaking the mechano-inflammatory cycle that drives OA progression. This article reviews the lubrication mechanisms of articular cartilage, the role of phospholipids in joint health, and recent advances in liposome-mediated drug delivery and lubrication restoration for OA treatment. It further highlights emerging strategies for integrating lubrication and anti-inflammatory functions into liposomal systems, and discusses key challenges and future directions toward personalized OA therapies.