Novel mucoadhesive montmorillonite/starch-graft-poly (methacrylic acid) nanocomposite hydrogels (Mt/S-g-PMAA) based on gelatinized wheat starch, an anionic monomer methacrylic acid (MAA), and different amounts of montmorillonite (Mt) as nanoparticles were synthesized according to the conventional grafting reaction mechanism in the aqueous media. The grafting amount of the products (G%) was determined. The formation of Mt/S-g-PMAA was confirmed by FTIR and XRD analyses. The swelling behavior and the erosion characteristics of the Mt/S-g-PMAA were investigated in deionized water, and pH = 5 lactate buffer solution as in vitro vaginal medium at 37 +/- 0,1 degrees C. Mechanical and in vitro mucoadhesion properties of all Mt/S-g-PMAA were also investigated using ewe vaginal mucosa. The results show that adding a higher amount of Mt could effectively increase the mucoadhesion properties of the clay mineral-polymer nanocomposite (CPN) hydrogels. It is then concluded that the 10Mt/S-g-PMAA may be used as alternative highly mucoadhesive CPN hydrogel drug carrier for vaginal route. (C) 2015 Elsevier B.V. All rights reserved.