(194s) Sizing Drug Delivery Particles in Blood Plasma

Designing particles for successful drug delivery requires knowledge of how the particle will behave in the body. Once injected into the blood stream, often nanoparticles are rapidly removed by the immune system and accumulate in the liver instead of the intended target. Some research has been done to improve particle circulation by tuning the size of the nanoparticle to less than 200 nm and by modifying the surface, such as by adding poly(ethylene glycol) (PEG) ligands. Little is known how these factors affect the behavior of the particles in the blood as there are few tools available to directly study particles in blood.

To accurately size particles, dynamic light scattering (DLS) is frequently used. DLS works well with clean, monodisperse samples. However is does not work well to measure particles in blood as the components of blood also scatter light. To measure the extent of protein corona formation on particles, the particles are exposed to blood plasma then washed or diluted until DLS measurements can be done to measure the increase in particle size. By washing or diluting the particles, the loosely bound soft corona is removed and the measurements do not reflect what the particle would experience in vivo. As an alternative, we have developed a method of analyzing nanoparticles in blood plasma using nanoparticle tracking analysis (NTA) with fluorescent filters. By using fluorescently labeled particles, particles can be analyzed in complex solutions such as blood plasma. The size of the particle, and thus the size of the protein corona, can be measured in 100% blood plasma using this method. In this work, polystyrene particles incubated in blood plasma are measured using both DLS and NTA in pure blood plasma and in diluted blood plasma and the results from the two methods are compared. Surface modification is done to attach PEG ligands to the particles and the size of the particle is again measured in blood plasma using both DLS and NTA. PEGylating the particles does not appear to decrease the total size of the protein corona measured in pure blood plasma by NTA. The use of this characterization method will allow for better understanding of particle behavior in the body, and potential problems related to protein corona formation can be addressed before investing in in vivo studies to improve the efficacy of drug delivery particles.