Surface charge shifting mixed micelles to overcome intestinal drug delivery barriers
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<sub>90:10</sub> > PME_DOTAP<sub>80:20</sub>). Upon ALP-mediated phosphate cleavage, mixed micelles exhibited a pronounced zeta potential shift (Δ50.1 mV for PME_DOTAP<sub>90:10</sub>; Δ38.8 mV for PME_DOTAP<sub>80:20</sub>). 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.
Authors
- Dennis To
- Annika Postina (ORCID: https://orcid.org/0000-0002-6793-2772)
- Andreas Bernkop‐Schnürch (ORCID: https://orcid.org/0000-0003-4187-8277)
- M H Ebert
- Katrin Zöller
Institutions
- Universität Innsbruck (AT)
Publication Details
- Journal
- Colloids and Surfaces B Biointerfaces
- Published
- 2025-09-23
- DOI
- https://doi.org/10.1016/j.colsurfb.2025.115148
- Primary Topic
- Advanced Drug Delivery Systems
- Type
- article
- Field-Weighted Citation Impact
- 0.00