Size of Nanoparticles

The biodistribution pattern of nanoparticles, active nanoparticle targeting to tumor antigens, and passive nanoparticle targeting by EPR91 are all greatly effected by the size of the nanoparticle. Passive targeting of the nanoparticle occurs because microvasculatures of tumors are more "leaky," thus permitting selective permeation of nanoparticles into the desired tumor tissue. This phenomenon has been exploited to target liposomes, therapeutic and diagnostic nanoparticles, and drug-polymer conjugates to cancer tissue (reviewed by Maeda).91 Smaller particles (fewer than 150 nm) are better suited for permeating through the leaky microvasculature of the tumor cells, and their more pronounced surface curvature may also reduce interaction with the receptors on the surface of macrophages and subsequent clearance of the particles.12 Biodistribution studies using liposomes have shown that although particles that are larger than 200 nm are largely taken up by the spleen, those less than 70 nm are also efficiently cleared by the liver.92 Taken together, the optimal nanoparticle size should be experimentally determined for each formulation because the interplay of various parameters (polymer system, encapsulated drug, surface charge, surface modification) makes it difficult to extrapolate the ideal nanoparticle size from seemingly similar studies. In our laboratory, we have tuned the size of polymeric nanoparticles made either by emulsions or nano-precipitation to study the best formulation for a specific application. Generally, one can make use of the interaction of different solvents used for making the emulsions or tune the size of the nano-particle by adjusting solvent ratios and polymer concentrations in solution. Our biodistribution studies using various sizes of poly(lactic-co-glycolic acid) (PLGA)-PEG nanoparticle-aptamer bioconjugates, has suggested a linear relationship with regards to uptake by liver and spleen such that smaller particles (~ 80 nm) are modestly better at avoiding uptake by these organs (unpublished results).

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