Surfactants bearing monophosphate esters with PEG of increasing chain length and different lipophilic tail structures were investigated to improve the effectiveness of enzyme triggered charge-converting nanoemulsions.
The surfactants PEG-8-stearate, PEG-22-tocopheryl succinate (TPGS), PEG-3-oleate, PEG-9-oleate and PEG-9-lauryl ether were phosphorylated and incorporated in a self-emulsifying drug delivery system (SEDDS) exhibiting a defined PEG corona. To provide a positive zeta potential increasing amounts of the cationic surfactant benzalkonium chloride (BA) were incorporated. The effect of these PEG monophosphate esters (P-PEG-surfactants) was evaluated based on enzyme induced phosphate release and change in zeta potential.
Significant enzyme induced charge conversion was observed for all P-PEG-surfactants, showing shifts from Δ 3 mV to Δ 31 mV. Surfactants comprising the shortest and longest PEG chain showed similar amplitudes (P-PEG-3-oleate: Δ 11.9 mV; P-PEG-22-TPGS Δ 10.2 mV), whereas P-PEG-8-stearate, P-PEG-9-oleate and P-PEG-9-lauryl ether bearing similarly long PEG chains but different lipophilic tail structures resulted in pronounced differences in amplitudes of Δ 10.3 mV, Δ 14.5 mV and Δ 18.1 mV, respectively. Furthermore, an indirect correlation between the lipophilicity of P-PEG-surfactants and the obtained charge-reversing effect was observed. With the exception of P-PEG-lauryl ether, this charge-reversal effect decreased with increasing BA concentrations.
In conclusion, the enzyme induced amplitude of charge conversion of P-PEG-surfactants depends to a high extent on their lipophilic tail structure. Based on this knowledge potent charge-reversal nanoemulsions can be designed.