Microanalysis of DDS Nanoparticle by Polarization Interferometric Nonlinear Confocal Microscopy

Nanoparticulate drug delivery systems (DDS) have attracted a lot of attention because of their size- and dopant-dependent properties. Nano formulations can be tailored to meet a wide range of product requirements dictated by... [ view full abstract ]

Nanoparticulate drug delivery systems (DDS) have attracted a lot of attention because of their size- and dopant-dependent properties. Nano formulations can be tailored to meet a wide range of product requirements dictated by disease condition, route of administration and considerations of cost, product stability, toxicity and efficacy. Researchers have an array of tools for DDS particle analysis, including scanning, transmission or atomic force microscopy (SEM/TEM/AFM); dynamic light scattering (DLS); nuclear magnetic resonance (NMR); and sundry spectrometry techniques, but they all have a variety of limitations, including complex sample preparation or the difficulty of analyzing enough particles to get a statistically significant result. Additionally, the analysis for sometimes must be performed even in preservation liquid solutions.
Now, we focus on spectroscopic analysis of a single polymer DDS nanoparticle with a polarization-interferometric nonlinear confocal microscope to analyze the nanoparticle in high CTF (Contrast Transfer Function). Unlike fluorescent microscope, the microscope proposed has an advantage in nondestructive and noncontact evaluation without doping toxic dye probes. Introducing the Michelson-type polarization-vector interferometry enhances the spatial contrast resolution of the confocal system both in axial and lateral directions. There are two typical ways to use the interferometer: on the one hand, when the analyzer axis in front of a confocal pinhole is set at near 45°, the microscope functions as the positive-type one to add the signals of s- and p-scattering components; but, on the other hand, when the analyzer axis is set at near 135°, the microscope functions as the negative type one to subtract the signals of the two components. Here, in the negative type one, we set the confocal signal minimum while scanning the background; a tiny χ(3) area shines out against the dark background with high contrast.
We measured three-dimensional inhomogeneous distribution in a single 200-nm particle with the microscope that performs the electric field subtraction of the scattered light from medium and the reference light. We have succeeded in evaluating dopant distribution in the DDS nanoparticle (see figure). Also, polarization analysis estimated the molecular density, molecular orientation and refractive index difference between major and minor axes.