Thiolation of non-ionic surfactants for the development of lipid-based mucoadhesive drug delivery systems

Abstract

The aim of this study was to develop thiolated self-emulsifying drug delivery systems (SEDDS) and nanostructured lipid carriers (NLCs) with improved mucoadhesive properties. Two non-ionic surfactants bearing a short and long PEG chain, namely polyoxyethylene (10) stearyl ether (PSE10) and polyoxyethylene (100) stearyl ether (PSE100), were thiolated for the first time by substituting the terminal hydroxyl group with a thiol group. The synthesis was confirmed by FT-IR, NMR and Ellman’s test. SEDDS and NLCs containing these thiolated compounds were investigated for size, polydispersity index (PDI) and ζ potential. Subsequently, mucus diffusion studies, rheological evaluations after mixing the nanocarriers with mucus and mucoadhesion studies on porcine intestinal mucosa were performed. All nanocarriers had a size less than 250 nm, a maximum PDI of 0.3 and a ζ potential < −9.0 mV. Mucus diffusion studies resulted in the rank order of increasing diffusivity: PSE10-SH < PSE100-SH < PSE10-OH < PSE100-OH for NLCs and PSE10-OH < PSE100-OH < PSE100-SH < PSE10-SH for SEDDS. The mucoadhesive properties and increase in viscosity of SEDDS and NLCs ranked: PSE100-OH < PSE10-OH < PSE100-SH < PSE10-SH. In addition, the short chain PSE10-SH showed higher mucus interactions than the long chain PSE100-SH for both SEDDS and NLCs. The thiolated PSE surfactants appeared to be promising excipients for the design of highly mucoadhesive drug delivery systems.