Nanoparticle Tracking Analysis of Polymer Nanoparticles in Blood Plasma

• Published in: Particle & particle systems characterization Vol. 38; no. 6
• Main Authors: Bannon, Mark S., López Ruiz, Aida, Corrotea Reyes, Karen, Marquez, Miriam, Wallizadeh, Zahra, Savarmand, Mohammad, LaPres, Connor A., Lahann, Joerg, McEnnis, Kathleen
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 01.06.2021
• Subjects: Agglomeration; Blood plasma; Coronas; Drug delivery systems; nanoparticle tracking analysis; Nanoparticles; particle aggregation; Photon correlation spectroscopy; Plasma; polystyrene nanoparticles; Polystyrene resins; protein corona; Proteins; Tracking
• ISSN: 0934-0866; 1521-4117
• DOI: 10.1002/ppsc.202100016

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. Interaction between nanoparticles and proteins is one of the major limitations for drug delivery systems. This work presents a methodology based on nanoparticle tracking analysis (NTA) to characterize this interaction. Fluorescently labeled nanoparticles can be imaged using NTA to characterize the entire protein corona in undiluted plasma. Due to the unique visualization of NTA, multicomponent aggregation can also be quantified.