Synthesis, characterisation, and in vitro assessment of hyaluronic acid-coated solid lipid nanoparticles entrapping dexamethasone palmitate designed for intra-articular administration.

Osteoarthritis (OA) is the major cause of pain and disability worldwide, particularly affecting the knee joint. Although intra-articular (IA) treatments including corticosteroids and hyaluronic acid (HA), are commonly used to manage symptoms, their therapeutic effects are often short-lived, necessitating repeated injections. In this study, HA-coated solid lipid nanoparticles (HA-DXP-SLNs) entrapping with the glucocorticoid prodrug, dexamethasone palmitate (DXP) was developed as dual-function nanocarrier system for IA delivery. Using a scalable microfluidics platform, monodisperse SLNs of ∼90 nm in diameter were produced with high DXP encapsulation efficiency (88%) and loading capacity (6% w/w). In phosphate buffered saline (PBS), DXP-SLNs exhibited a biphasic release profile with an initial burst followed by sustained release of DXP, which was further moderated by HA surface coating. HA coatings of the SLNs enhanced particle stability, shifted particle surface charge from positive to negative, and enabled uptake by patient-derived primary osteoarthritic chondrocytes (hOAAC). Incubation in murine plasma demonstrated enzymatic conversion of DXP to dexamethasone (DEX), which accumulated in plasma over 72 h. HA-DXP-SLNs suppressed prostaglandin E2 production by LPS-stimulated THP-1 monocytes and by hOAAC more effectively than uncoated DXP-SLNs, while maintaining cell viability. These findings indicate that the HA coating of SLNs contributes to in vitro therapeutic efficacy of the overall SLNs, as well as to particle stabilisation. HA-DXP-SLNs therefore represent a promising nanocarrier for prolonged IA corticosteroid delivery in knee OA, with the potential to reduce the frequency of current IA corticosteroid and HA administration.