The two types of particles in particulate drug delivery systems are micro- and nanoparticles, measured in micrometers and nanoparticles respectively. This size difference accounts for differing engineering applications for the two types of particles.

Because nanoparticles are smaller than microparticles, they have a greater proportion of their bodies that is exposed to the surrounding aqueous phase, meaning they will have a greater loss of payload and a lower maximal drug loading. Smaller particles are more likely to aggregate and have better binding than large ones. After injection, microparticles in tissue have a tendency to remain where they have been placed. Nanoparticles in the same tissue, however, showed complete clearance. This property of microparticles can be used to intentionally obstruct blood flow. Nanoparticles, on the other hand, are too small to cause clotting and can circulate throughout the bloodstream. Nanoparticles can cross biological barriers and can be used as passive targeting. Microparticles, however, must be delivered directly to the site of interest. Microparticles can only be delivered into cells that are phagocytic, while nanoparticles can be delivered to all kinds of cells. This property of microparticles suggests that they can be utilized for passive targeting to antigen presenting cells. Understanding particle migration post-injection is important because most particles will elicit an acute inflammatory response if particulate material is present after 7-14 days.

Local delivery often favors the use of larger particles. Generally, larger particles are more capable of achieving longer durations of nerve blockade through sustained release by factors such as higher drug loading, longer time to degradation, and complete drug release. Smaller particles are unable to achieve such long durations. Nanoparticles have a tendency to leave their delivery site, although this can be prevented by using hydrogels. Larger particles are less likely to leave on the long term. This application can be used to treat a body surface or cavity.

In systemic delivery, smaller particles are favored to avoid rapid or non-specific clearance from the bloodstream. Micro- and nanoparticles require different physiological parameters to act as filters; for example, five-micrometer particles will passively target phagocytic antigen presenting cells. Microparticles cannot cross the blood-brain barrier, while the possibility of doing so for nanoparticles is still being investigated.