Effect of Thiolated Polymers on Caco-2 Cell Permeability of Vinca Alkaloids

Abstract This study aimed to evaluate the influence of glutathione-based systems—poly(acrylic acid)-glutathione (PAA-GSH), chitosan-glutathione (ch.GSH), and free glutathione (GSH)—on the intestinal permeability of vingerbine alkaloids. The transepithelial transport of herbamine, herbadine, and vincarine was investigated using the Caco-2 cell monolayer model. Apical-to-basolateral and basolateral-to-apical fluxes were measured in the presence of PAA-GSH, ch.GSH, or free GSH to assess their effects on absorptive permeability and efflux-related processes. PAA-GSH significantly enhanced apical-to-basolateral transport, increasing permeability by 3.4-, 2.59-, and 1.52-fold for herbamine, herbadine, and vincarine, respectively, consistent with thiol-mediated reversible modulation of epithelial tight junctions. In contrast, ch.GSH reduced absorptive transport (1.28-, 1.67-, and 1.51-fold) and markedly decreased basolateral efflux, suggesting polymer–drug complex formation and reduced availability of free drug. Free GSH showed minimal influence on alkaloid permeability. These findings demonstrate that polymer architecture critically determines the intestinal transport behavior of vingerbine alkaloids. PAA-GSH acts as an effective permeation enhancer and represents a promising carrier for improving the intestinal delivery of tested compounds. Future studies will focus on developing optimized delivery systems for this anti-arrhythmic agent.