Physicochemical Properties of Nanoparticles and Their Effect on Transport across the Microvasculature

In the past couple of decades nanomedicine has become a well-defined area of interdisciplinary science, in which advances in nanotechnology are allowing the incorporation of multiple therapeutic, sensing and targeting agents into nanostructured materials. This is reflected by the large number of promising nanomedical formulations being currently evaluated by the US Food and Drug Administration. A problem with many, if not all of these, is that mathematical modeling, as a tool to narrow the design parameter space to obtain an optimal formulation, is not part of the design process. Adoption of these tool will bring nanomedicine closer to pharmaceutics, a field in which mathematical modeling has been an essential part of the design process for many years. Nanoparticle delivery occurs mainly through the microvasculature, comprised of arterioles, capillaries, and venules ranging in diameter from 100 to 300 µm, 5 to 10 µm, and 7 to 50 µm, respectively. The study of how nanoparticle design parameters affect their transport properties as it pertains to targeting and drug delivery has become a growing field in the development of nanomedical formulations. The physicochemical properties of nanoparticles, such as size, shape and surface charge can be optimized to improve their performance in these applications. For instance, it allows modulation of interactions with the immune system, better control over blood clearance and interactions with target tissue, permitting effective delivery of payload within cells or tissues. Their ability to target and enter tissues from the microvasculature is highly dependent on their behavior under blood flow. Here we present a review of the current approaches to mathematical modeling of nanoparticle transport across the vasculature and its effects on targeting efficacy. center of the showing Adhesion Model developed for Ligand-receptor pair to Model showed that for a 50% predicted probability of adhesion with increased NP diameter there is a need for an increased amount of ligands in order to bind to the vessel wall; Design maps were created to show where adhesion occurs and can provide how to design NPs based upon size, surface characteristics of ligand-receptor density and affinity and how to prevent NP endocytosed.