Pressure gradients in solid tumors

Abstract

In order to reach target cells, nanoparticles must transport through the systemic circulation, extravasate from blood vessels, and penetrate the interstitial tissue. These transport processes occur by a combination of convection and diffusion. Tissue pressure gradients play an integral role in directly and indirectly mediating the convective and diffusive transport of nanoparticles in solid tumors. Specifically, poorly regulated tissue pressure gradients reduce the micro-regional delivery, extravasation, and penetration of nanoparticles. In this chapter we discuss the pathogenesis of abnormal tissue pressure gradients in solid tumors, describe their influence on the enhanced permeability and retention (EPR) effect, nanoparticle drug delivery, and review methods to modulate tissue pressure gradients to improve the transport of nanoparticles in solid tumors.