alpha-phenyl-N-tert-butyl nitrone (PBN) is a neuroprotective free radical scavenger however it has low in vivo stability and blood residence time. Aim of this study is to develop a nanoparticle formulation by using different polymeric system which enhance the blood residence tune and in vivo stability of PBN and characterize in terms of particle size, zeta potential, morphology, encapsulation efficiency, in vitro release profiles. Chitosan (CS). poly(D,L-lactide-co-glycolide) (PLGA) and their poly(ethylene glycol) (PEG) block co-polymers were used for comparative study. Results showed that particle sizes of CS, CS-PEG, PLGA and PLGA-PEG nanoparticles are between 142-356 nm. PLGA nanoparticles and their block-copolymers' nanoparticle have greatly monodisperse distribution. CS and CS-PEG nanoparticles have zeta potential values between 17-40 mV related to amine groups, contrariwise PLGA and PLGA-PEG nanoparticles have negative zeta potential in the range of (-8)-(-19) mV. Encapsulation efficiency and loading capacity for all formulations are between 12-54 %, 9-68 %, respectively. PLGA-PEG nanoparticles are promising for further studies due to their sufficient encapsulation efficiency and in vitro release profiles.