Aim: Comparison of the impact of polyethylene glycol (PEG) and polyglycerol (PG) surface decoration on self-emulsifying drug delivery system (SEDDS)-membrane interaction and cellular uptake. Materials & methods: PEG-, PEG/PG- and PG-SEDDS were assessed regarding their self-emulsifying properties, surface charge, bile salt fusibility, cellular uptake and interaction with endosome-mimicking membranes. Results: SEDDS exhibited droplet sizes between 150 and 175 nm, a narrow size distribution and self-emulsified within 7 min. Higher PEG-surfactant amounts in SEDDS resulted in charge-shielding and thus in a decrease of ζ potential up to Δ11 mV. The inert PEG-surface hampered bile salt fusion and interfered SEDDS–cell interaction. By reducing the PEG-surfactant amount to 10%, cellular uptake increased twofold compared with PEG-SEDDS containing 40% PEG-surfactant. PG-SEDDS containing no PEG-surfactants showed a threefold increased cellular uptake. Furthermore, complete replacement of PEG-surfactants by PG-surfactants led to enhanced cellular interaction and improved disruption endosome-like membranes. Conclusion: PG-surfactants demonstrated high potential to address PEG-surface associated drawbacks in SEDDS.
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