ABSTRACT
Biological barriers to drug transport prevent successful accumulation of nanotherapeutics specifically at diseased sites, limiting efficacious responses in disease processes ranging from cancer to inflammation. Although substantial research efforts have aimed to incorporate multiple functionalities and moieties within the overall nanoparticle design, many of these strategies fail to adequately address these barriers. Nanoparticle-based drug delivery platforms have emerged as suitable vehicles for overcoming pharmacokinetic limitations associated with conventional drug formulations. Margination dynamics, or the lateral drift of nanoparticles to endothelial walls, is a very important nanoparticle design consideration, as association with vessel walls favors particle-cell binding and receptor-ligand interactions in active targeting strategies and enables extravasation through the fenestrated vasculature of tumors. Although improvements in patient safety and morbidity led to clinical approval of nanoparticle platforms, such as doxorubicin and paclitaxel, efficacious patient responses remain modest; currently, these platforms offer only marginal improvements over conventional formulations.
