Abstract: Chitosan (CS)/Quinazolinone/Tripolyphosphate (TPP) nanoparticles have been synthesized using 2.3:1 molar ratio of CS/TPP in presence of quinazolinone derivatives (I-IV) through simple one step reaction. The mixture was subjected to ultrasonic waves to obtain the nanoparticles. The nanoparticles are quite uniform in size, spherical shape and rod like structure depending on the quinazolinone derivatives. The amount of loaded quinazolinone was calculated using UV-Vis spectrophotometer and TGA. The release of quinazolinone derivatives (I-IV) in acidic medium (pH=2) is significantly higher than in slightly acidic medium (pH=6.8). The proposed mechanism based on zero orders, first order, Higuchi, Hixson-Crowell and Korsmeyer-Peppas model equation are explored. The antimicrobial activity of nanoparticles was investigated against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus epidermis and Staphylococcus aureas.