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

The aim of this study was to develop thiolated self-emulsifying drug delivery systems (SEDDS) and nano -structured 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 zeta 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 zeta 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.

Automated summary

This study aimed to develop thiolated self-emulsifying drug delivery systems (SEDDS) and nano-structured lipid carriers (NLCs) with improved mucoadhesive properties. Thiolated PSE surfactants were found to be promising excipients for the design of highly mucoadhesive drug delivery systems.