Rat synovial tissue and blood rapamycin pharmacokinetics after intra-articular injection of free solution or nanoparticles vs free rapamycin intravenous shot

•Rapamycin seems chondroprotective, but its distribution may produce side effects.•Articular injection of tailored nanoparticles (NPs) may avoid systemic diffusion.•We injected 10 μM of free rapamycin (RAPA) vs RAPA-loaded NPs in rat knees.•RAPA-loaded NPs joint delivery is biocompatible, extending synovium residency.•Joint RAPA-loaded NPs lower blood levels and reduce harmful systemic exposure.