Surface charge shifting mixed micelles to overcome intestinal drug delivery barriers
Year: 2025
Type: article
Abstract: This study aimed to develop micelles with synergistic properties for mucus permeation and enhanced cellular uptake. Micelles consisted of C12-15 alcohol 3 ethoxylate phosphate ester (PME) whereas mixed micelles additional contained 1,2-dioleoyloxy-3-trimethylammonium-propane chloride (DOTAP) in molar ratios 90:10 and 80:20. Physicochemical and toxicity properties of micelles were investigated. Further evaluation of alkaline phosphatase (ALP)-associated mucus permeation, phosphate release, zeta potential shift and subsequent cellular uptake of the model compound fluorescein dilaurate (FDL) was conducted. All micelles showed strong mucus-permeating behaviour, with permeability enhanced up to 18-fold (PME > PME_DOTAP 90:10 < PME_DOTAP 80:20 ). Upon ALP-mediated phosphate cleavage, mixed micelles exhibited a pronounced zeta potential shift (Δ50.1 mV for PME_DOTAP 90:10 ; Δ38.8 mV for PME_DOTAP 80:20 ). This shift was directly linked to increased membrane interaction and resulted in a 7- to 10-fold improvement in cellular uptake of FDL. Together, these findings identify PME_DOTAP mixed micelles as promising oral delivery systems that combine efficient mucus permeation with enzyme-triggered uptake enhancement. • Phosphorylated micelles achieve strong mucus permeation efficiency • Enzyme-triggered phosphate release induces micelle charge shifting • Enzyme-responsive micelles allow localized intestinal drug release • Mixed micelles enhance intracellular delivery • Synergistic micelles overcome mucus and cell barriers for oral delivery
Authors: Annika Postina, Dennis To, Katrin Zöller, Melanie Lena Ebert, Andreas Bernkop-Schnürch
Institution: Universität Innsbruck
Language: English
Subfield: Pharmaceutical Science
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $3,790
OpenAlex ID: W4414447256