BACKGROUND: IN RECENT YEARS CHITOSAN (CS), A NATURAL-ORIGIN POLYSACCHARIDE, IS BIODEGRADABLE, NON-TOXIC AND SOFT-TISSUE COMPATIBLE, AND THUS HAS BEEN USED EXTENSIVELY IN BIOMEDICAL APPLICATIONS [1]. MOLECULAR DYNAMIC SIMULATIONS FOUND THAT A DEGREE OF SUBSTITUTION (DS) OF 5% OF PALMITOYL GROUPS ON ITS BACKBONE WAS SUFFICIENT TO ALLOW NPCS TO FORM NANOPARTICLES (NPS), DUE TO A SIGNIFICANT INCREASE IN THE INTRA AND INTERMOLECULAR HYDROPHOBIC INTERACTIONS [1]. IN THE PRESENT WORK, THE NPS PREPARED BY THE SYNTHESIZED NPCS POLYMERS WITH DIFFERENT DS. IN THE STUDY, TO INCREASE DS THE SYNTHESIZED NPCS WAS ANALYZED BY THE (1H NMR) AND (FT-IR) SPECTROSCOPY OF THE FORMED HYDROGEL WAS EXAMINED BY (SEM) AND (TEM). RHEOLOGY EXPERIMENTS WERE PERFORMED TO INVESTIGATE THE VISCOELASTIC PROPERTIES OF AQUEOUS NPCS AT DIFFERENT PH, TEMPERATURE, AND SHEAR RATE ENVIRONMENTS.METHODS: A MIXTURE OF CS AND AQUEOUS ACETIC ACID (50 ML, 2% W/V) WAS STIRRED FOR 24 H TO ENSURE TOTAL SOLUBILITY. THE PH WAS ADJUSTED TO 6.0 BY SLOW ADDITION OF 1 N NAOH AND THE FINAL VOLUME OF CS SOLUTION WAS 100 ML. A SOLUTION OF PALMITIC ACID N-HYDROXYSUCCINIMIDE ESTER IN ABSOLUTE ETHANOL WAS ADDED DROPWISE TO THE CS SOLUTION AT 97OC AND REACTED FOR 40 H. SUBSEQUENTLY, THE PREPARED SOLUTION WAS COOLED AT ROOM TEMPERATURE, ADDED 20 ML ACETONE, AND PRECIPITATED BY ADJUSTING ITS PH VALUE TO 12.0. THE PRECIPITATE (NPCS) WAS THEN FILTERED, WASHED WITH AN EXCESS OF ACETONE, AND AIR-DRIED. THE DS ON NPCS WAS DETERMINED BY FT-IR.RESULTS: IN THE STUDY DS INCREASING FROM 2.1% TO 5.7% WITH OPTIMUM TEMPERATURE 97OC, PH 12.0. AND TIME REACTION 40 H INDO N2. DS (%)=[(A1650 / A3455)- 0.12]* 100, DS IS THE VALUE 0.12 REPRESENTS THE ACETYL GROUPS SPECIFIED IN NATIVE CHITOSAN.CONCLUSION: THE EXTENT OF CELLULAR UPTAKE OF NPS WAS SIGNIFICANTLY ENHANCED WITH INCREASING THE DS ON NPCS FOR USE ASEXCIPIENTS IN CONTROLLED DRUG DELIVERY SYSTEMS. HYDROPHOBIC INTERACTIONS ARE BELIEVED TO ENHANCE THE STABILITY OF SUBSTITUTED CHITOSAN. IT SUGGESTED THAT THE RELEASE OF DRUG IS CONTROLLED BY DIFFUSION, DEPENDING ON BOTH THE ACYL CHAIN LENGTH AND THE DEGREE OF DS.