Single particle optical extinction and scattering allows real time quantitative characterization of drug payload and degradation of polymeric nanoparticles

Abstract

The behavior of nanoparticles in biological systems is determined by their dimensions, size distribution, shape, surface chemistry, density, drug loading and stability; the characterization of these parameters in realistic conditions and the possibility to follow their evolution in vitro and in vivo are, in most of the cases, far from the capabilities of the standard characterization technologies. Optical techniques such as dynamic light scattering (DLS) are, in principle, well suited for in line characterization of nanoparticle, however their fail in characterizing the evolution of nanoparticle in solution where change in particle dimension and density is present. Here we present an in-line optical technique based on single particle extinction and scattering (SPES) overcoming the limitations typical of DLS and allowing for the efficient characterization of nanoparticle polydispersity, index of refraction and degradation dynamics in solution. Using SPES, we characterized the evolution of PLGA nanoparticles with different structures and drug payloads in solution and we compared the results with DLS. Our results suggest that SPES could be used as a process analytical technology for pharmaceutical nanoparticle production.

Using single nanoparticle tracking obtained by nanophotonic force microscopy to simultaneously characterize nanoparticle size distribution and nanoparticle–surface interactions

“…This intricacy of characterization combined with the need for detailed understanding of the particle dispersion presents a significant technical challenge to the community. Examples of new technologies used to address these issues are single particle optical extinction and scattering 44 and analytical ultracentrifugation 45 . Here we report a further development of the existing NFM technique to simultaneously measure the size distribution of a NP sample and its interaction potential with a surface.…”

Detecting the shape of anisotropic gold nanoparticles in dispersion with single particle extinction and scattering

“…This overcomes the limitations typical for DLS, making SPES an efficient tool for the in line characterisation of nanoparticle polydispersity in fluids, providing information on particle size distribution, agglomeration state and refractive index of the dispersed species. [26][27][28][29][30][31] In the present configuration, SPES can work with dielectric particles down to roughly 200 nm in diameter. In the case of metallic NPs, as for example gold, both scattering and extinction efficiencies are much larger than in the case of dielectric particles, increasing the sensitivity of the method for small sizes.…”

“…These two independent parameters are directly measured from the interference between the transmitted beam and the forward scattered light, thanks to the self-reference interference between the faint scattered and the intensely transmitted fields. 27,28 The raw data generated by SPES are described with real and imaginary parts of the electric field, Re S(0) and Im S(0) respectively. [27][28] The former is related to the ability of the particle to scatter and absorb the light and the latter to the capacity of the particle of being polarized under an external field, i.e.…”

“…27,28 The raw data generated by SPES are described with real and imaginary parts of the electric field, Re S(0) and Im S(0) respectively. [27][28] The former is related to the ability of the particle to scatter and absorb the light and the latter to the capacity of the particle of being polarized under an external field, i.e. polarizability.…”

“…[27][28] A 5 mW solid state laser (wavelength 635 nm) has been focused to a diameter of 5 µm into a flow cell and the emerging light collected by a segmented photodiode. A small particle passing through the focal region generates a scattered wave that superimposes to the intensely transmitted beam.…”