Nanoparticle Tracking Analysis of Polymer Nanoparticles in Blood Plasma

A successful drug delivery system must overcome complex biological barriers. For particles injected into the blood, one of the first and most critical barriers pertains to blood stability to circulate through the human body. To effectively design drug delivery vehicles, interactions between the particles and blood, as well as the aggregation behavior, must be understood. This work presents a method to analyze particle size and aggregation in blood plasma using a commercially available nanoparticle tracking analysis (NTA) system. As a model system, fluorescently labeled polystyrene nanoparticles are incubated in goat blood plasma and analyzed using NTA. The particles incubated in plasma are found to have a protein corona that is larger than what has been observed by dynamic light scattering (DLS) in diluted plasma. Particles that are decorated with a PEG layer are also found to have large protein coronas in undiluted plasma. Because NTA is based on a unique visualization method, large multicomponent aggregates could be observed and quantified in a manner not feasible with other techniques. PEGylation of the particles is found to decrease the multicomponent aggregation from 1000 ± 200 particles for unmodified to 200 ± 30 particles for 1K PEGylated per 1 × 10⁵ total particles.