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Hydrogels exhibiting Volume Phase Transition (VPT) are considered as useful biomaterials for the preparation of various drug delivery systems. Such hydrogels are commonly based on thermo-responsive polymers, such as poly(2-(2-methoxyethoxy)ethyl methacrylate) (PMEO2MA), that have lower critical solution temperature (LCST) in aqueous solutions. In this work, PMEO2MA hydrogels were used as model systems to study the influence of encapsulated drugs, such as ibuprofen and salicylate sodium salts, on the temperature and dynamics of the VPT. Both thermo-optical analysis and differential scanning calorimetry have shown that the VPT becomes broader and shifts towards higher temperatures with increasing drug concentration. Three regimes of VPT in PMEO2MA gels were distinguished. The first two, related to the breaking of the strong water–polymer interactions and to the network collapse, slow down with increasing drug concentration. The last regime, corresponding to the slow diffusion of a residual solution from a collapsing network, becomes visible only for systems with high content of drug. Raman spectroscopy studies show that the observed effect is not connected to direct interactions between polymers and drugs. This suggests that the drug molecules are able to stabilise water–polymer interactions in thermo-responsive hydrogels. Consequently, they are able to modulate VPT and have a significant influence on the delivery process. [ABSTRACT FROM AUTHOR]