Differential role of plasma proteins between humans and common animal models on the adhesion efficiency of VTCs
Katawut Namdee, Peter J. Onyskiw, Daniel J. Sobczynski, Omolola Eniola-Adefeso
Vascular-targeted drug carrier (VTC) interaction with plasma has been recognized as a critical factor in determining its targeted adhesion efficiency in vitro. However, the differential role of plasma proteins between humans and common animal models on the adhesion efficiency of VTCs in vitro has yet to be investigated. In this study, a parallel-plate flow chamber (PPFC) assay is used to directly measure the binding efficiency of VTCs in rabbit, porcine, mouse, and human blood flow and for all particles tested, adhesion was observed to be drastically reduced in porcine blood/plasma flows relative to PBS buffer control. However, relative adhesion between mouse blood and buffer was increased/maintained for all nanoparticles. The use of non-fouling poly(ethylene)-glycol (PEG) coating at ultra-high density was able to practically eliminate the impact of plasma proteins on the adhesion of microparticles, but not nanoparticles. Overall, our results suggest that porcine models, as opposed to the murine models, better model the performance of VTCs in terms of their vascular wall adhesion and thus can serve as a better model for predicting the in vivo functionality of drug carriers in the clinic. These considerations hold great importance for the design of various pharmaceutical products, and likely will lead to more efficient and reliable drug delivery systems.