Polymer nanoparticles have been widely studied as possible drug delivery systems due to their ability to control the release of drug contained within them and due to their biocompatibility [1,2]. They are relatively easy to produce with their drug release profiles dependent upon polymer structure. Some of the important characteristics of polymer nanoparticles for drug delivery applications include their particle size and surface chemistry. Typically, they range in size from 10 to 1000nm in diameter allowing them to transverse cell membranes.
There are a variety of ways in which delivery of encapsulated drug from polymer nanoparticles can be controlled [1]. These include physical (e.g. sonorphoresis), chemical (e.g. pH, salt concentration), biochemical (e.g. enzyme) and environmental (e.g. temperature) mechanisms. The influence of these mechanisms on the size of the polymer nanoparticles can be investigated using dynamic light scattering (DLS).
Dynamic light scattering is a non-invasive technique for measuring the size of colloidal dispersions and molecular solutions. In the technique, a sample is contained in a suitable cuvette and illuminated with a laser beam. The resulting scattered light fluctuates in intensity due to the random, Brownian motion of the particles. An analysis of these intensity fluctuations through autocorrelation allows for the determination of the diffusion coefficients, which in turn yield the particle size through the Stokes-Einstein equation [3-5].
A sample of polymer nanoparticles dispersed in water was measured on a Zetasizer Nano ZS using a temperature range of 50 to 90oC at 1oC intervals. A delay time of 5 minutes was used at each temperature to ensure that the sample viscosity was equilibrated before the measurements were taken. The Zetasizer Nano ZS uses a 4mW He-Ne laser operating at a wavelength of 633nm with a detection angle of 173°. The detection angle of 173o allows for size measurements of concentrated, turbid samples.
Figure 1 is a plot showing the effect of temperature on the mean count rate (in kilo counts per second (kcps) and z-average diameter (in nanometres) of the polymer nanoparticle dispersion. The z-average diameter is the intensity-weighted mean diameter obtained from the cumulants analysis as defined in ISO13321 [4] and ISO22412 [5] and is sensitive to the presence of aggregates, large particles or any changes which occur in the size of sample being measured.
Figure 1: Effect of temperature on the mean count rate (in kilo counts per second (kcps) and z-average diameter (in nanometers)
The data in Figure 1 shows that the z-average diameter increases with increasing temperature. Normally, an increase in the z-average diameter is an indication of particle aggregation. This would also result in an increase in the mean count rate. However, in the results obtained in this study, the mean count rates decrease upon heating. Therefore, the increase in the mean diameter indicates that the polymer particles are swelling with increasing temperature. As the conformation of these swollen particles becomes more open with increasing temperature, the refractive index of particles decreases (i.e. the relative refractive index decreases) with a resultant decrease in the mean count rate.
The results contained in this application note demonstrate that dynamic light scattering can be used to investigate the influence of temperature on the behavior of polymer nanoparticles. In this example, an increase in temperature has resulted in the swelling of polymer nanoparticles causing an increase in their size and a decrease in the scattering intensity.
[1] D. Bennet and K. Sanghyo (2014) Polymer nanoparticles for smart drug delivery, Application of Nanotechnology in Drug Delivery 8, 257-310.
[2] Y. Kawashima (2001) Nanoparticulate Systems for Improved Drug Delivery, Advanced Drug Delivery Reviews 47, 1-2.
[3] R. Pecora (1985) Dynamic Light Scattering: Applications of Photon Correlation Spectroscopy. Plenum Press, New York.
[4] International Standard ISO13321 (1996) Methods for Determination of Particle Size Distribution Part 8: Photon Correlation Spectroscopy. International Organization for Standardization (ISO).
[5] International Standard ISO22412 (2008) Particle Size Analysis: Dynamic Light Scattering (DLS). International Organization for Standardization (ISO).
