In this contribution, a novel smart drug delivery system (DDS) consisting of hydroxyl-functionalized glycerol poly(ecaprolactone)(PGCL)-based microspheres and poly(N-isopropylacrylamide) (PNIPAAm) hydrogel was developed for prolongedand sustained controlled drug release. Various amounts PGCL-based microspheres were incorporated physically into temperaturesensitive poly(N-isopropylacrylamide) (PNIPAAm) hydrogel to form the novel DDSs. Resulting DDSs were characterized byscanning electron microscopy (SEM), differential scanning calorimetry (DSC), and compression modulus measurements toinvestigate the morphological, thermal, and mechanical properties. The temperature dependence of swelling ratio and responsekinetics upon heating or cooling were also investigated to understand the smart properties, i.e., temperature sensitive properties ofthese DDSs. Finally, ovalbumin (OVA), used as the model drug, was loaded into PGCL-based microspheres to examine andcompare the effects of controlled release at different temperature (22 and 37 1C) of these novel smart DDSs.