Synthesis and in vitro characterization of a novel poly(acrylic acid)-glutathione conjugate

The purpose of the present study was to improve the multifunctional properties of poly(acrylic acid) by the covalent attachment of glutathione. The adhesive properties of poly(acrylic acid)-glutathione (PAA-GSH) conjugate were evaluated in vitro on freshly excised porcine mucosa via tensile studies and the rotating cylinder method. The permeation enhancing effect of the conjugate in combination with glutathione was evaluated in Ussing chambers by using sodium fluoresceine as model compound. The resulting PAA-GSH conjugate displayed 353.7 ± 41.8 (n = 3) μmol immobilized free thiol groups and 309.8 ± 27.3 (n = 3) μmol disulfide bonds per gram polymer. In aqueous solutions, the modified polymer demonstrated improved cohesive properties. Due to the immobilization of glutathione, the swelling velocity of the polymer was 4-fold accelerated. Tensile studies showed that the mucoadhesive properties of poly(acrylic acid) were strongly improved by the covalent attachment of glutathione. The adhesion time of PAA-GSH was more than 14-fold higher in comparison to unmodified poly(acrylic acid). Furthermore, the conjugate exhibited a 1.77-fold higher permeation enhancing effect compared with the control. According to the results of the present study, PAA-GSH conjugate represents a very promising novel thiomer for the development of various mucoadhesive drug delivery systems.