Self-Emulsifying Drug Delivery Systems Changing Their Zeta Potential Via a Flip-Flop Mechanism Publisher Pubmed



Salimi E^{1, 6} ; Levinh B^{2, 4} ; Zahirjouzdani F^{2, 3} ; Matuszczak B⁵ ; Ghaee A¹ ; Bernkopschnurch A²
Source: International Journal of Pharmaceutics Published:2018

Abstract

To overcome the mucus layer and cell membrane barrier, self-emulsifying drug delivery systems (SEDDS) exhibiting negative zeta potential, switching to positive values when having reached the cell membrane is a promising approach. Accordingly, a novel conjugate was synthesized by covalent attachment of phosphotyrosine to octadecylamine, which was incorporated into SEDDS. Generated system presented an average diameter of 32 nm and zeta potential of around −12 mV when being diluted 1:100 in 100 mM HEPES buffer pH 7.5 containing 5 mM MgCl2 and 0.2 mM ZnCl2. Incubation of SEDDS with isolated intestinal alkaline phosphatase (IAP) resulting in enzymatic cleavage of phosphate ester moiety caused a shift in zeta potential up to +5.3 mV. As non-toxicity of the developed SEDDS diluted 1:1000 in 25 mM HEPES buffer pH 7.5 containing 5% glucose was observed on Caco-2 cells by employing resazurin assay, this system may provide an inspiring strategy for future zeta potential changing drug delivery systems to master the mucus and membrane barrier. © 2018 Elsevier B.V.