Figure 4.

In vivo pharmacokinetic study of Cy5-conjugated μPLs (Cy5-μPLs) in a PTOA mouse model. (a) Representative pharmacokinetic time course intravital images (skin on) and ex vivo knee images (skin off) of Cy5-μPLs injected intra-articularly into PTOA mouse knee joints (D-#, where # represents days after intra-articular injection); (b) Intravital fraction of retention of Cy5-μPLs plotted as mean + standard error. Note = the initial uptick in fluorescence within the joints in the first couple of hours after injection is a result of loss of fluorophore self-quenching, which occurs due to high-density fluorophore conjugation onto the particles; (c) Anatomically labeled sagittal section of a mouse knee joint 1 day after intra-articular injection showing the Cy5-μPLs dispersed across the joint interacting and/or in close proximity to many different tissue types such as the cartilage, the infrapatellar fat pad and synovium, and the joint capsule; (d) Confocal microscopy imaging performed 1 day after intra-articular injection showing Cy5-μPLs located on top of the cartilage surface, near the cartilage/synovium interface, and the joint capsule. In all images, the scale bar = 100 μm; (e) Confocal microscopy imaging of Cy5-μPLs within the mouse knee joint taken at different time points after intra-articular injection. TD = transmission detector. NT = no treatment. For intravital imaging analysis, n = 4–24 limbs depending on the time point, that is, earlier time points had more animals included, and the sample size at the later time points was lower because some animals were taken down at earlier time points for ex vivo and confocal microscopy analysis. For ex vivo imaging analysis and confocal microscopy analysis, n = 2–4 limbs per time point.