S-protected thiolated surfactants enhancing surface properties of lipid-based nanocarriers

This work aimed to investigate the influence of surface decoration of orally administered lipid-based nanocarriers (LNCs) through S-protected thiolated surfactant on key properties such as mucodiffusion, adhesion and cellular uptake. This comparative study with simple thiolation was performed on chemically modified polyoxyethylene stearyl ether (PSE) surfactant with different PEG chains exhibiting free thiol groups, which were subsequently protected by mercaptonicotinic acid or cysteine. Successively, nanostructured lipid carriers (NLCs) and solid lipid nanoparticles (SLNs) were decorated with thiolated PSE surfactants and their impact on the formulations was evaluated through in-vitro studies on intestinal mucosa. Characterization studies on mucus diffusion and adhesion were first performed to assess the ability of LNCs to reach the adsorption epithelia. Then, cellular uptake and endosomal escape analysis showed the successful performance of the cysteine-protected thiolate surfactant-based samples in being the more taken up among the investigated decoration and to evade from the adopted endosome model. Furthermore, the results confirmed that the PEG chain length determines the efficacy of the produced systems, showing that shorter polymer chain length corresponds to better cellular uptake. Hence, considering the obtained results, the samples resulting from the adoption of PSE10-Cys could represent interesting nanosized vehicles for drug delivery in mucosal tissues.