Poly(N-isopropylacrylamide-co-maleic acid) (poly(NIPAAm-co-MAc)) with an appropriate comonomer ratio was designed and synthesized as an appealing pH/thermo-responsive copolymer. In simulated physiological fluids (phosphate buffer solution (PBS) at pH = 7.4 and T = 36 degrees C), both carboxylic groups of MAc in copolymer (pK(a1) = 3.45, pK(a2) = 6.09) are in the ionized form, more hydrophilic and consequently the copolymer loses the thermosensitive properties. However, when the carboxylate groups present in the copolymer are protonated or interact ionically with positively-charged compounds with hydrophobic character (e.g. diphenhydramine, DPH), the copolymer takes back the thermosensitive properties at the physiological pH and temperature. Therefore, microgels obtained from poly(NIPAAm-co-MAc) are in the swollen state in PBS at T = 36 degrees C, i.e. they are in the "inactive" state. However, after ionic interactions with hydrophobic compounds, taken as triggering agents, the microgels become "activated" and collapse. Therefore, the triggering agent is the key factor controlling the thermosensitivity of the hydrogel. (C) 2017 Elsevier Ltd. All rights reserved.