Nanoparticle delivery and particle diffusion in confined and complex environments

Multiple biological, chemical and physical factors influence and dictate the success or otherwise of nanocarrier mediated drug delivery and targeting. One issue is diffusion. This review considers aspects of the movement of nanoparticles in their passage from the selected point of administration to their intended locus of action, with an emphasis on the effects of particle diffusion in the often confined and complex spaces of the body. Diffusion of drugs and carriers rarely takes place in free unbounded spaces in vivo, it being more likely to occur, in part at least, in complex, heterogeneous locations, for example between villi and microvilli in the intestine, in the extracellular matrix of tumours and in the crowded environment of cell interiors. Flow in capillaries involves changing pressures, changing capillary radii and asymmetric bifurcations of vessels. Nanocarrier passage through pores and fenestrae in the process of extravasation, which itself is a stochastic process, may be impeded by particle jamming thus hindering procession towards cellular goals. While many of these processes have been difficult to study in vivo, there are many basic studies of these phenomena which can be applied to the biological situation. This overview examines diffusion-related phenomena and speculates on their importance in attaining the still elusive goal of achieving a significant proportion of the administered dose of nanoparticles (and hence drug) in target tissues.