Zeta potential changing nanoemulsions: Impact of PEG-corona on phosphate cleavage

The aim of this study was to evaluate the impact of a PEG-corona on oily droplets of a nanoemulsion on phosphate cleavage on their surface. A PEG-free nanoemulsion composed of 60% oleic acid, 30% Capmul MCM EP and 10% Span 85 being additionally stabilized by 1% cetyltrimethylammonium bromide (CTAB) and 3% phosphatidic acid (PA) was evaluated regarding phosphate release, zeta potential change and mucus permeation properties. In order to evaluate the impact of PEG-corona on phosphate release 10%, 20% and 30% of polyethoxylated-35 castor oil were incorporated in the nanoemulsion. The developed PEG-free nanoemulsion exhibited the droplet size of 123 nm with PDI of 0.24, whereas the droplet size of the nanoemulsions containing PEG ranged from 166 nm to 128 nm with PDI about 0.26. In case of the PEG-free formulation enzymatically induced phosphate cleavage was 3-fold and 7-fold higher than that from formulations containing 20% and 30% PEG-surfactant, respectively. Accordingly, the zeta potential shift of PEG-free formulation reached ~Δ 40 mV within 4 h, whereas zeta potential of PEG-containing formulations did not show any significant changes remaining constant at ~-30 mV. In contrast, PEG-containing formulations exhibited a 3.3-fold to 4-fold higher mucus permeation than the PEG-free formulation. According to the results, a PEG-corona has a great impact on phosphate cleavage and zeta potential change, which has to be taken into consideration for the development of highly efficient zeta potential changing nanocarriers, as zeta potential constitutes one of the crucial parameter regarding the permeation properties through physiological barriers.