Implication of particle-by-particle characterization of nanoparticle dispersions for in vitro testing
Anoop K Pal
Harvard T.H. Chan. School of Public Health, USA
: Forensic Toxicol Pharmacol 2015, 4:3
Abstract
Over past decades, nano-bio research has essentially been focused on studying the underlying mechanisms of nano-bio interactions, their potential nano-environment health and safety implications (Nanotoxicology) as well as utilizing this knowledge for designing better therapeutics (Nanomedicine). In vitro assessment of nanoparticles (NP) and nano-formulations is the most common testing platform for evaluating biological responses, which requires prior NP dispersion, stabilization, and characterization in cell culture media. Dispersion inefficiencies and active aggregation of particles often result in polydisperse size distributions. Accurate characterization of important properties of such polydisperse distributions (size distribution, effective density, charge, mobility, aggregation kinetics, etc.) is critical for understanding differences in the effective dose delivered to cells as a function of time and dispersion conditions, as well as for nano–bio interactions. Here, standardized dispersion and dosimetry platform was used for preparing NP dispersions and estimating the delivered dose to cells based on dispersion characterization input from dynamic light scattering (DLS) and tunable resistive pulse sensing (TRPS), for a set of 8 distinct nanomaterials. The TRPS technology offers higher resolution and sensitivity compared to DLS and provides unique insights into NP size distribution and concentration, as well as particle behavior and morphology in complex culture media. The overall relative in vitro toxicity ranking for 8 NP types changed considerably, matching notably better the in vivo inflammation data (R 2 = 0.97 versus 0.64). These findings further reinforce the need to reanalyze and reinterpret in vitro data in the light of dispersion and dosimetry considerations (or lack thereof ) and to adopt these standardized protocols for future in vitro assessment studies.
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