Abstract

Elucidation of the structural properties of colloids is paramount for a successful formulation. However, the intrinsic dynamism of colloidal systems makes their characterization a difficult task and, in particular, there is a lack of physicochemical techniques that can be correlated to their biological performance. Nanoparticle tracking analysis (NTA) allows measurements of size distribution and nanoparticle concentration in real time. Its analysis over time also enables the early detection of physical instability in the systems not assessed by subtle changes in size distribution. Nanoparticle concentration is a parameter with the potential to bridge the gap between in vitro characterization and biological performance of colloids, and therefore should be monitored in stability studies of formulations. To demonstrate this, we have followed two systems: extruded liposomes exposed to increasing CHCl3 concentrations, and solid lipid nanoparticles prepared with decreasing amounts of poloxamer 188. NTA and dynamic light scattering (DLS) were used to monitor changes in nanoparticle number and size, and to estimate the number of lipid components per particle. The results revealed a strong negative correlation between particle size (determined by DLS) and concentration (assessed by NTA) in diluted samples, which should be adopted to monitor nanocolloidal stability, especially in drug delivery.

Highlights

  • Colloids are defined as complex systems composed of solid particles dispersed in a liquid, governed by a high internal kinetic energy[1]

  • For liposomes submitted to the complete extrusion cycle (6 times), the particle sizes observed were 162.5 ± 1.4 nm by dynamic light scattering (DLS) and 162.4 ± 2.8 nm by nanoparticle concentration (NTA) (Fig. 1A), with polydispersity index (PDI)

  • The simple premise that significant changes in particle size and distribution indicate instability of a colloidal system formed the basis of our hypothesis

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Summary

Introduction

Colloids are defined as complex systems composed of solid particles dispersed in a liquid, governed by a high internal kinetic energy[1] They are widely studied in biological, food and environmental fields, and Ostwald said ‘all life processes take place in a colloidal system’[2]. Accelerated or long-term study of physicochemical stability must be performed for those formulations[4] Parameters such as particle size and distribution are followed over time by particle-tracking approaches based on the Brownian motion principle[5], such as photocorrelation spectroscopy/dynamic light scattering (DLS), laser diffraction analysis and nanoparticle tracking analysis (NTA). Until 2011, only two works had employed the number of nanoparticles as a parameter to evaluate nanotoxicity in ecotoxicity/environmental studies, against 18 others that compared DLS and NTA in the characterization of particle size and distribution[9]

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