Hyaluronic acid–functionalised solid lipid nanoparticles for enhanced oral uptake and therapeutic efficacy in rheumatoid arthritis

The aim of present work was to develop and optimise hyaluronic acid-functionalised, chloroquine-loaded solid lipid nanoparticles (HA-CQL-SLNs) for CD44 receptor-mediated therapy of rheumatoid arthritis. The Chloroquine base was precipitated and characterised using UV spectroscopy, FTIR, and DSC. Solid lipid nanoparticles were prepared by melt emulsification followed by probe sonication and optimised using a Box-Behnken design. Particle size, polydispersity index, zeta potential, and entrapment efficiency were evaluated. Ex vivo intestinal uptake was assessed using endocytosis inhibitors, while in vivo pharmacokinetic studies with cycloheximide pretreatment evaluated lymphatic transport. Therapeutic efficacy was studied in arthritic rats. The optimised HA-CQL-SLNs showed a particle size of 412.8 ± 0.71 nm, zeta potential of -9.6 ± 2.3 mV, and entrapment efficiency of 94.6 ± 0.49% (w/w). The lymphatic uptake involved clathrin- and caveolae-mediated endocytosis which was established by reduced systemic drug exposure in animals receiving Cycloheximide pre-treatment. HA-CQL-SLNs significantly reduced paw oedema and joint damage. Thus it can be concluded that HA-CQL-SLNs enhanced bioavailability and therapeutic efficacy, demonstrating potential as a targeted oral delivery system for rheumatoid arthritis.