Novel nanostructured, high transparent, and pH sensitive poly(2-hydroxyethyl methacrylate-co-methacryliac acid)/poly(vinyl alcohol) (P(HEMA-co-MA)/PVA) interpenetrating polymer network (IPN) hydrogel films were prepared by precipitation copolymerization of aqueous phase and sequential IPN technology. The first P(HEMA-co-MA) network was synthesized in aqueous solution of PVA, then followed by aldol condensation reaction, it formed multiple IPN nanostructured hydrogel film. The film samples were characterized by IR, SEM, DSC, and UV-vis spectrum. The transmittance arrived at 93%. Swelling and deswelling behaviors showed the multiple IPN nanostructured film had rapid response. The mechanical properties of all the IPN films improved than that of PVA film. Using crystal violet as a model drug, the release behaviors of the films were studied. The results showed that compared with PVA, which had low drug loading and exhibited high and burst release, the three IPN films had high drug loading and exhibited sustained release. Besides, the release followed different release mechanism at pH = 4.0 and pH = 7.4, respectively. (C) 2009 Wiley, Periodicals, Inc, J Appl Polym Sci 112: 2261-2269, 2009