Factors affecting the clearance and biodistribution of polymeric nanoparticles

Abstract

Nanoparticle (NP) drug delivery systems (5-250 nm) have the potential to improve current disease therapies because of their ability to overcome multiple biological barriers and releasing a therapeutic load in the optimal dosage range. Rapid clearance of circulating nanoparticles during systemic delivery is a critical issue for these systems and has made it necessary to understand the factors affecting particle biodistribution and blood circulation half-life. In this review, we discuss the factors which can influence nanoparticle blood residence time and organ specific accumulation. These factors include interactions with biological barriers and tunable nanoparticle parameters, such as composition, size, core properties, surface modifications (pegylation and surface charge), and finally, targeting ligand functionalization. All these factors have been shown to substantially affect the biodistribution and blood circulation half-life of circulating nanoparticles by reducing the level of nonspecific uptake, delaying opsonization, and increasing the extent of tissue specific accumulation.

Figure 1

Nanoparticle platforms for drug delivery. Polymeric nanoparticle platforms are characterized by their physicochemical structures, including polymerosome, solid polymeric nanoparticle, nanoshell, dendrimer, polymeric micelle, and polymer−drug conjugates.

Figure 2

Biodistribution and clearance of polymeric nanoparticles. Tissue defects, stealth properties, targeting, and the size of the nanoparticles are major factors affecting the biodistribution and clearance of polymeric nanoparticles.