Biomedical and Chemical Engineering Research Seminar Series - Designing Better Drug Delivery Particles: Nanoparticle Tracking Analysis of Particles in Blood Plasma

Designing Better Drug Delivery Particles: Nanoparticle Tracking Analysis of Particles in Blood Plasma

Drug delivery particles must overcome many biological barriers to successfully reach their target. One of those challenges is to evade the immune system and circulate through the body until they find their intended target. Many different engineered particles have been used to improve the circulation time of particles such as by adding poly(ethylene glycol) (PEG) ligands, adding zwitterionic polymers, adjusting particle size and shape, and attaching peptides to the surface. Though some of these tactics have resulted in longer circulation times, there is still significant off-site accumulation of the particles. It is difficult to determine why off-site accumulation occurs and how changes to the particle surface affect it as there are very few tools available to directly study particles in blood. We have developed a method of analyzing particles in blood plasma using nanoparticle tracking analysis (NTA) using fluorescently labeled particles. The size of the particle, and thus the size of the protein corona, can be measured in pure blood plasma using this method. Additionally, due to the unique visualization of the nanoparticles, the aggregation behavior of the particles in blood plasma can be observed and quantified. In this work, polymer particles incubated in blood plasma are measured using NTA in pure blood plasma. Surface modification is done to attach PEG ligands of different molecular weights to the particles and the size of the particle is measured in blood plasma using NTA resulting in surprisingly large protein coronas on all particles. However, the aggregation behavior of the particles is significantly improved using PEG ligands. The use of this characterization method will allow for testing of engineered particles for drug delivery directly in blood plasma to determine the features that improve behavior in the blood. 

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