Zeta potential changing self-emulsifying drug delivery systems utilizing a novel Janus-headed surfactant: A promising strategy for enhanced mucus permeation

Abstract

AimThe aim of this study was to develop zeta potential changing self-emulsifying drug delivery systems (SEDDS) utilizing a Janus-headed surfactant in order to improve mucus permeation. Methods12-Amino-1-dodecanol (12-AD) was phosphorylated by utilizing phosphorus pentoxide (P2O5) and incorporated in a concentration of 2% into a SEDDS formulation (10% Glycerol 85, 30% Campul MCM, 30% Cremophore EL, 30% Captex 355). The phosphorylated 12-AD (p-12-AD) loaded SEDDS were characterized regarding their size and zeta potential. Phosphate release studies from SEDDS having been diluted 1:100 in HEPES buffer were performed with isolated alkaline phosphatase (10 U/mL) as well as cell-associated intestinal alkaline phosphatase (AP). In parallel, the resulting change in zeta potential as well as the increase in amino group concentration on the surface of SEDDS were monitored. The effect of zeta potential change on mucus permeation was evaluated by Transwell method with freshly isolated porcine mucus utilizing fluorescein diacetate (FDA) as a marker. ResultsSize and zeta potential of SEDDS were 61 ± 3.8 nm and −9.37 mV, respectively. The amount of phosphate release was 29.91 μmol/g and 1.22 μmol/g in the presence of isolated AP and Caco-2 cell monolayer, respectively. SEDDS showed a shift in zeta potential from −9.37 mV to +0.5 mV in the presence of isolated AP within 6 h. The mucus permeation results demonstrated that negatively charged SEDDS permeate the mucus gel layer to a 6.5-fold higher extent than SEDDS having already changed their zeta potential to positive because of phosphate cleavage. ConclusionSEDDS containing a Janus-headed phosphorylated surfactant might be a promising strategy for mucosal drug delivery.