Synthesis and physico-chemical investigation of thiolated dextran derivative: Design and application of a redox-responsive drug delivery system

In the present investigation, redox-responsive-based dextran carriers were developed for the controlled release of hydrophobic molecules via a reducing agent naturally present in cells, namely glutathione. In this sense, dextran was modified with a thiol derivative. The roles of the hydrophilic segments in the molecular self-organisation of polysaccharide derivatives into nanoparticles were investigated by varying the average dextran molar mass. Crosslinked thiolated dextran particles were good carriers of hydrophobic molecules such as Nile red dye, which were efficiently encapsulated in the hydrophobic core and then selectively released. Indeed, the disulfide linkage connecting the hydrophobic tail with dextran was found to be cleaved by glutathione under physiological conditions for the fast release of Nile red. The cytotoxicity of the dextran-based particles was examined, and it was found to be nontoxic to living cells. Finally, we explored the versatility of dextran-derived particle drug carriers for pancreatic cancer treatment. The designed carriers were loaded with the anticancer drug paclitaxel and the obtained particles exhibited redox-responsive drug release and excellent anticancer activities with up to 90 % inhibition of cancer cell viability. Thus, the developed dextran derivatives are highly promising and suitable for a wide range of biomedical applications that require the loading and release of hydrophobic compounds.