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

[Display omitted] 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 (PSE 10) and polyoxyethylene (100) stearyl ether (PSE 100), 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: PSE 10 -SH < PSE 100 -SH < PSE 10 -OH < PSE 100 -OH for NLCs and PSE 10 -OH < PSE 100 -OH < PSE 100 -SH < PSE 10 -SH for SEDDS. The mucoadhesive properties and increase in viscosity of SEDDS and NLCs ranked: PSE 100 -OH < PSE 10 -OH < PSE 100 -SH < PSE 10 -SH. In addition, the short chain PSE 10 -SH showed higher mucus interactions than the long chain PSE 100 -SH for both SEDDS and NLCs. The thiolated PSE surfactants appeared to be promising excipients for the design of highly mucoadhesive drug delivery systems. [ABSTRACT FROM AUTHOR]