For big particles (>1 μm), particle shape plays a dominant role in phagocytosis by macrophages as the uptake of particles is strongly dependent on the local shape at the interface between particles and APCs [174]. Worm-like particles with high aspect ratios (>20) exhibited negligible

phagocytosis compared to spherical particles [175]. On the other hand, spherical gold nanoparticles (AuNPs) (40 nm) were more effective in inducing antibody response than other shapes (cube and rod) or Selleck 5FU the 20 nm-sized AuNPs, even though the rods (40 nm × 10 nm) were more efficient in APC uptake than the spherical and cubic AuNPs [59]. A number of studies also reported the effect of hydrophobicity, showing higher immune response for hydrophobic particles than hydrophilic ones [176] and [177]. A number of other factors such as surface modification (pegylation, targeting ligands) and vaccine cargo [45] have been shown to affect the interaction between nanoparticles and APCs as well. Designing safe and efficacious nanoparticle vaccines requires a thorough understanding of the interaction of nanoparticles with biological systems which then determines the fate of nanoparticles in vivo. Physicochemical properties of

nanoparticles including size, shape, surface charge, and hydrophobicity influence the interaction of nanoparticles with plasma proteins [178] and [179] and immune cells [176]. These interactions as well as morphology of vascular endothelium play an important role in distribution of nanoparticles in various organs and tissues of the body. Selleckchem GSK-3 inhibitor The lymph node (LN) is a target organ for vaccine delivery since cells of

the immune system, in particular B and T cells, reside there. Ensuring delivery of antigen to LNs, by direct drainage [180] and [181] or by migration of well-armed peripheral APCs [182], no for optimum induction of immune response is therefore an important aspect of nanoparticle vaccine design. Distribution of nanoparticles to the LN is mainly affected by size [183] and [184]. Nanoparticles with a size range of 10–100 nm can penetrate the extracellular matrix easily and travel to the LNs where they are taken up by resident DCs for activation of immune response [184], [185], [186] and [187]. Particles of larger size (>100 nm) linger at the administration point [181], [186] and [188] and are subsequently scavenged by local APCs [181], [187] and [189], while smaller particles (<10 nm) drain to the blood capillaries [184] and [189]. The route of administration and biological environment to which nanoparticles are exposed could also affect the draining of nanoparticles to the LN. It was reported that small PEG coated liposomes (80–90 nm) were significantly present in larger amounts in LNs after subcutaneous administration as compared to intravenous and intraperitoneal administration [190].