Phosphate decorated lipid-based nanocarriers providing a prolonged mucosal residence time

Abstract

The aim of this study was to develop phosphate decorated lipid-based nanocarriers including self-emulsifying drug delivery systems (SEDDS), solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC) to extend their mucosal residence time. All nanocarriers contained tetradecyltrimethylammonium bromide (TTAB) and polyoxyethylene (9) nonylphenol monophosphate ester (PNPP) for surface decoration. Zeta potential, cytotoxicity, charge conversion and phosphate release studies using isolated intestinal alkaline phosphatase (IAP) and Caco-2 cells were performed. Moreover, the residence time of nanocarriers was determined on porcine intestinal mucosa. Results showed a shift from negative to positive zeta potential due to the addition of TTAB and charge conversion back to a negative zeta potential when also PNPP was added. Up to a concentration of 0.3 %, lipid-based nanocarriers were not toxic. Charge conversion studies with IAP revealed the highest zeta potential shift for NLCTTAB-PNPP with almost Δ22 mV. Phosphate release studies using isolated IAP as well as Caco-2 cells showed a fast phosphate release for SEDDSTTAB-PNPP, SLNTTAB-PNPP and NLCTTAB-PNPP. SLN TTAB-PNPP and NLC TTAB-PNPP provided the highest increase in mucosal residence time that was 4-fold more prolonged than that of blank formulations. In conclusion, phosphate modified lipid-based nanocarriers can essentially prolong the intestinal residence time of their payload.