Intra-articular drug delivery strategies aiming to deliver drugs in diseases affected by cartilage-related issues are using electrostatic interactions to penetrate the dense cartilage matrix. This enables delivery of sufficient drug concentrations to the chondrocytes to mediate the desired therapeutic effect. As it is well known that size and charge of nanoparticles affects its interactions with the surrounding biological fluids, where proteins adsorb to the NP surface, resulting in a protein corona. There are, however, no studies investigating how the formed protein coronas affect cartilage uptake and subsequent cellular uptake, nor how they affect other cells present in the synovium of such diseases. Here, we explore the differences between the protein coronas that form when NP are incubated in synovial fluid from osteoarthritic and rheumatoid arthritis patients and compare this to results obtained using fetal calf serum (FCS), as guide for researchers working on joint drug delivery. We demonstrate that the protein corona indeed affects the uptake into cartilage, where there are major differences between the model proteins in fetal calf serum, as compared to synovial fluid from rheumatoid arthritis patients as well as osteoarthritis patients. The data suggests that when developing drug delivery vehicles for joint diseases that leverages electrostatic interactions and size, the interactions with proteins in the biological milieu is highly relevant to consider.
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