Highly thiolated corn starch for enhanced mucoadhesion and permeation

This study explores the mucoadhesive and permeation enhancing properties of highly thiolated corn starch as a potential excipient for mucosal drug delivery. Native corn starch was chemically thiolated using phosphorous pentasulfide in sulfolane. The degree of thiolation was quantified by Ellman's test and the chemical structure was confirmed using ¹H NMR, FTIR spectroscopy, and Differential Scanning Calorimetry (DSC). Cytotoxicity was evaluated using the resazurin viability assay. Thiolated starch was evaluated regarding swelling power, viscosity, and mucoadhesion. Mucoadhesive properties were investigated through rheological analysis with intestinal mucus, tensile testing on porcine intestinal tissue, and mucosal residence time studies. Thiolated starch with 1658 μmol/g thiol groups showed no cytotoxicity up to a concentration of 0.2 mg/ml after 24 h of incubation. Rheological evaluations demonstrated a 3.5-fold increase in dynamic viscosity for the thiolated starch-mucus mixture compared to native starch. Thiolated starch showed a 91.1-fold enhancement in mucoadhesion as compared to unmodified starch. Tensile testing revealed a 4.3-fold increase in maximum detachment force and a 2.5-fold increase in total work of adhesion. Furthermore, Permeation studies using sodium fluorescein (Na-Flu) as a marker demonstrated a 2-fold higher permeation enhancing effect on freshly excised rat intestinal mucosa in comparison to unmodified starch. Because of its mucoadhesive and permeation enhancing properties, highly thiolated starch might be a promising excipient for mucosal drug delivery.