February 24, 2021 – Do PEG solutions have excess nanoparticles, and should vaccine makers be concerned?
Recent reports (see here or here) of severe allergic reactions in people receiving the COVID-19 vaccines point to the possibility of an anaphylactic response due to nanoparticles present in PEG (polyethylene glycol), a part of the lipid nanoparticle bubble that stabilizes the mRNA molecules in the vaccine.
As a leader in the innovation of nanoparticle analysis, we set out to design a simple experiment to quantify the amount of nanoparticles present in PEG using the Spectradyne nCS1TM particle analyzer. For our experiment, we prepared a 1 percent solution of PEG-200 in 1× PBS (phosphate buffer saline). The PBS diluent was filtered using a 20nm syringe filter to reduce the contribution of background particles.
We tested the 1% PEG-200 solution in our state-of-the-art microfluidic cartridges, C-400 and C-2000, to span a broad size range. We found significant number of nanoparticles below 1 micron in size contained in this PEG 200 solution, as shown in Figs. 1 and 2.
Figure 1. Large diameter measurement of nanoparticles concentration versus diameter, comparing a 1% PEG-200 solution with a 1% Tween-20 solution
Figure 2. Small diameter measurement of nanoparticles concentration versus diameter, comparing a 1% PEG-200 solution with a 1% Tween-20 solution
The figures reveals that in the upper size range from 280-2000nm (Figure 1, dark green curve), the concentration of particles in the 1% PEG 200 solution is 4.1 × 106 particles/mL, with a striking increase in concentration towards smaller diameters — something we see often in solutions that tend to form aggregates.
We can compare the concentration of particles in the 1% PEG solution to those present in a 1% Tween 20/PBS solution (light green curve) that has been filtered to 20nm. The particle concentration for the 1% Tween solution is measured to be 3.5 × 105 particles/mL, an order of magnitude lower than measured in the 1% PEG solution.
In the smaller size range from 65-250nm (see Figure 2) the particle concentration in the 1% PEG 200 solution is 1.48 × 108 particles/mL, compared to 5.7 × 107 particles/mL in the 1% Tween solution. Note the vertical scale in this figure is 250 times that used in Fig. 1. Again, the Tween solution has an order of magnitude fewer nanoparticles.
We have thus demonstrated that 1% PEG 200 solutions contain at least 108 particles/mL of nanoparticles below 1 micron in diameter. We hope this experiment provides valuable insight into the impact of PEG particles in the formulation process.
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