It was the aim of this study to evaluate the impact of lipases on the release behaviour of a peptide drug from oral self-nanoemulsifying drug delivery systems. Octreotide was ion paired with the anionic surfactants deoxycholate, decanoate, oleate and dodecylsulphate. The lipophilic character of these complexes was characterised by determining the n-octanol/buffer pH 7.4 partition coefficient. In the following the most hydrophilic complex was incorporated in a likely lipase degradable self-nanoemulsifying drug delivery systems (SNEDDS) formulation containing a triglyceride (olive oil; Pharm.Eur.) and in a likely not lipase degradable SNEDDS containing lipids and surfactants without any ester bonds. After 1: 100 dilutions in artificial intestinal fluid (AIF), the lipid droplets were characterised regarding size distribution. With these SNEDDS, drug release studies were performed in AIF with and without lipase. Results showed that the most hydrophobic complex can be formed with deoxycholate in an octreotide: anionic surfactant ratio of 1:5. Even 73.1 +/- 8.1% of it could be quantified in the n-octanol phase. SNEDDS containing octreotide vertical bar olive oil vertical bar cremophor EL vertical bar propylene glycol (2 vertical bar 57 vertical bar 38 vertical bar 3) and octreotide vertical bar liquid paraffin vertical bar Brij 35 vertical bar propylene glycol vertical bar ethanol (2 vertical bar 66.5 vertical bar 25 vertical bar 5 vertical bar 1.5) showed after dilution in AIF, a mean droplet size of 232 +/- 53 nm and 235 +/- 50 nm, respectively. Drug release studies showed a sustained release of octreotide out of these formulations for at least 24 h, whereas > 80% of the drug was released within 2 h in the presence of lipase in the case of the triglyceride containing SNEEDS. In contrast the release profile from ester-free SNEDDS was not significantly altered (p<0.05) due to the addition of lipase providing evidence for the stability of this formulation towards lipases. According to these results, SNEDDS could be identified as a useful tool for sustained oral peptide delivery taking an enzymatic degradation by intestinal lipases into considerations.