S-Protected thiolated nanostructured lipid carriers exhibiting improved mucoadhesive properties.

The purpose of the present study was to design nanostructured lipid carriers (NLCs) exhibiting improved mucoadhesive properties. First, an S-protected thiolated fatty acid conjugate was synthesized by amide bond formation between a primary amino group of l-cystine and palmitic acid N-hydroxysuccinimide. NLCs were prepared by nano-template engineering technique using Span 60, polysorbate 80, sucrose stearate and PEG 400 as surfactant mixture, stearic acid as solid lipid and miglyol as liquid lipid. NLCs were loaded with the model drug bergapten and decorated with the S-protected thiolated fatty acid conjugate. NLCs were characterized regarding particle size, poly-dispersity index (PDI), zeta potential, drug entrapment efficiency (EE), drug loading capacity (LC), drug release and mucoadhesive properties. Furthermore, cytotoxicity studies were performed on MDA-MB-231 cells via resazurin assay. S-Protected thiolated NLCs displayed a mean size of 115 nm, PDI of 0.3, zeta potential of -30 mV, 80% drug EE and 5% drug LC. Drug-loaded S-protected thiolated NLCs exhibited a sustained drug release and strongly enhanced mucoadhesive properties. Surface decoration with cystine substructures raised the cytotoxic potential of NLCs to a minor extent. Due to the immobilization of cystine substructures on the surface of NLCs, their mucoadhesive properties can be strongly improved.