The aim of this study is to synthesize microgels from combination of a functionalized natural based polymer, tragacanth gum (TG), and a synthetic copolymer, poly(methyl methacrylate-alt-maleic anhydride)-g-polycaprolactone, (poly(MMA-alt-MA)-g-PCL-C CH). Ring opening polymerization CROP) of epsilon-caprolactone (CL) in the presence of propargyl alcohol as initiator led to preparation of poly(alpha-propargyl -omega-hydroxyl)caprolactone (HO-PCL-C CH) which was grafted onto poly(MMA-alt-MA) to obtain amphiphilic block copolymer, poly(MMA-alt-MA)-g-PCL-C CH. Tosylated-TG was reacted with sodium azide to obtain TG-N-3 which then used in the click reaction with poly(MMA-alt-MA)-g-PCL-C CH to give amphiphilic conetwork (APCN) microgels. The copolymers and microgels were characterized using different techniques such as FT-IR, H-1 NMR, scanning electron microscope (SEM), zeta sizer and thermogravimetric analysis (TGA). The gel content of conetworks showed dependence on the weight ratio of poly(MMA-alt-MA)-g-PCL-C CH/TG-N-3. The swelling behavior of the prepared microgels showed dependence on the gel content, pH, immersion time, and temperature. Loading and in vitro release of quercetin as a model drug was investigated at pH 7. The total release showed dependence on the network structure of microgels and was in the range of 40-80% after 7 h. (C) 2014 Elsevier Ltd. All rights reserved.