One of the most important drawbacks of the thermosensitive hydrogels based on N-isopropylacrylamide (NIPAAm) is the lack of functional groups able to specifically bind drugs; moreover, these hydrogels are not biodegradable. In order to overcome these inconveniences, poly(NIPAAm-co-beta-cyclodextrin) (poly(NIPAAm-co-beta-CD)) microgels were obtained by cross-linking polymerization of the corresponding monomers. beta-CD was first functionalized with an appropriate amount of vinyl groups, thus acting both as a co-monomer with hosting properties and as a biodegradable cross-linker. The volume phase transition temperature (VPTT) of the microgels was determined under simulated physiological conditions by measuring the swelling degree and by microcalorimetry. The microgels, due to their small size and high porosity, possess a relative rapid swelling/deswelling rate around the human body temperature. The hydrogels were loaded with the model drug diclofenac by inclusion within cyclodextrin cavity and the release studies were performed under simulated physiological conditions, below and the above the VPTT. In the presence of a-amylase (from Aspergillus Oiyzae), microgels have showed a low degradation rate (15% of initial weight after 7 days), the erosion occurring especially at the surface. (C) 2014 Elsevier Ltd. All rights reserved.