Thiolated oligo and polysaccharides – next-gen drug delivery systems.

Abstract

For oral drug administration, the prolonged residence of drug carriers on mucosal surfaces offers significant benefits. This study introduces a novel thiolation method that allows a high degree of modification of oligo- and polysaccharides using phosphorus pentasulfide. The synthesized per-thiolated cyclodextrin demonstrated an 89-fold increase in mucoadhesion compared to the native oligosaccharide and a significantly extended residence time, both in vitro and in animal studies. Other natural polymers, such as starch and carrageenan, were also thiolated using this method, which greatly improved their mucoadhesive performance on buccal and intestinal mucosa. Additionally, thiolation enhanced cellular uptake, with up to a 20-fold increase in internalization compared to the native compound observed across different cell lines, followed by endosomal escape. The main drawback of thiolated polymers is their oxidative sensitivity, which we addressed by protecting the free thiols with reactive disulfides. Based on these findings, these new macromolecular drug carriers possess remarkable potential for both oral and parenteral use.