As hydrophobic drug carriers, chitosan (CS) and Starch (SR) were copolymerized as biodegradable nanohydrogel and were functionalized with pthalic-anhydride and hexamethylenetetramine via 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide catalyzed coupling, respectively. The structure, morphology, physicochemical and drug loading performance of native and functioned hydrogel were investigated by using several characterization techniques. With the successive functionalization the significant properties like porosity increases and crosslinking density decreases due to the formation of hydrophilic contacts with aqueous solutions. The FESEM analysis revealed the hydrogel matrices with uniform particle size, porosity and deep pores with high internal surface area for extreme swelling and interacting with the drug and biomolecules for efficient drug administration. The effect of induced functionalities on the physicochemical performance and release of hydrophobic- anionic model drug (Bromocresol green) were studied at physiological conditions. The drug release capability of the synthesized nanohydrogel was increased from 65% to 80% and 85% by successive functionalization. The drug administration in selective hydrogel was not significant, presumably due to stronger H-bonding and entanglement within the system which was finely tuned by the induced hydrophilic, flexible and biocompatible functionalities in term of extended interfaces for the drug solutions. The physicochemical and electrokinetic performances suggested the selective hydrogel as promising carriers for the hydrophobic- anionic drugs at physiological conditions.