Stearic acid modified biocompatible pullulan derivatives (PUSA1, PUSA2, PUSA3) with different degrees of substitution were synthesized via the reaction between the hydroxyl group of pullulan and carboxyl group of stearic acid (SA) in the presence of 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (EDC) and 4-dimethylaminopyridine (DMAP). The critical micelle concentration (CMC) were 50, 32, 18 μg/mL for PUSA1, PUSA2 and PUSA3 respectively, and transmission electron microscopy (TEM) images demonstrated that the self-assembled nanoparticles of PUSA made by dialysis method showed spherical shape. Doxorubicine (DOX), as a model drug, was loaded into the self-assembled nanoparticles of PUSA, and the highest encapsulation efficiency (84%) and drug loading content (7.79%) were achieved in PUSA3. The release of DOX in nanoparticles in vitro at pH 7.4 demonstrated slow sustained release over 90 h, while in the acidic environment, showed faster release. The study of cell cytotoxicity in vitro showed PUSA self-aggregated nanoparticles had no cell cytotoxicity even at high concentration of PUSA (1000 μg/mL). The uptake efficiency of PUSA/DOX, analyzed by flow cytometer and fluorescence, was rather higher than that of free DOX, which indicated that PUSA nanoparticles offer considerable potential as drug carriers for the efficient delivery of anti-cancer drugs.

Key words: stearic acid, pullulan, hydrophobicity-modified polysaccharide, self-assembled nanoparticle, drug delivery system