Self‐Emulsifying Drug Delivery Systems (SEDDS) Containing Reverse Micelles: Advanced Oral Formulations for Therapeutic Peptides

Abstract

Abstract Alternative methods to hydrophobic ion pairing for the formation of lipophilic complexes of peptide drugs to incorporate them in lipid‐based nanocarriers such as self‐emulsifying drug delivery systems (SEDDS) for oral administration are highly on demand. Such an alternative might be reverse micelles. Within this study, SEDDS containing dry reverse micelles (dRMs PMB ) formed with an anionic (sodium docusate; AOT), cationic (dimethyl‐dioctadecyl‐ammonium bromide; DODAB), amphoteric (soy lecithin; SL), or non‐ionic (polysorbate 85; P85) surfactant loaded with the model peptide drug polymyxin B (PMB) are developed. They are characterized regarding size, payload, release kinetics, cellular uptake, and peptide activity. SEDDS exhibit sizes from 22.2 ± 1.7 (AOT‐SEDDS‐dRMs PMB ) to 61.7 ± 3.2 nm (P85‐SEDDS‐dRMs PMB ) with payloads up to 2% that are approximately sevenfold higher than those obtained via hydrophobic ion pairing. Within 6 h P85‐SEDDS‐dRMs PMB and AOT‐SEDDS‐dRMs PMB show no release of PMB in aqueous medium, whereas DODAB‐SEDDS‐dRMs PMB and SL‐SEDDS‐dRMs PMB show a sustained release. DODAB‐SEDDS‐dRMs PMB improves uptake by Caco‐2 cells most efficiently reaching even ≈100% within 4 h followed by AOT‐SEDDS‐dRMs PMB with ≈20% and P85‐/SL‐SEDDS‐dRMs PMB with ≈5%. The peptide drug maintains its antimicrobial activity in all SEDDS‐dRMs PMB . According to these results, SEDDS containing dRMs might be a game changing strategy for oral peptide drug delivery.