Preparation Of Self-assembled Nanoparticles Of Stearic Acid Modified Pullulan Derivatives And Application As Novel Carriers Of Drug Delivery

Stearic acid modified biocompatible pullulan derivatives (PUSA1-3.80, PUSA2-4.08, PUSA3-5.41) with different degrees of substitution (DS) were synthesized via the reaction between the hydroxyl group of pullulan and carboxyl group of stearic acid in the presence of1-(3-Dimethylaminopropyl)-3-ethyl-carbodiimide hydrochloride (EDC) and4-Dim-ethylaminopyridine (DMAP). The structures of PUSA were confirmed by FTIR and1H NMR analysis. The morphology and size distribution of PUSA self-assembled nanoparticels prepared with the dialysis method were observed using dynamic laser light scattering (DLS) and transmission electron microscopy. The critical micelle concentration (CMC) of PUSA was measured with pyrene as a fluorescent probe. The experimental results show that PUSA self-assembly nanoparticles had a homogeneously spherical shape, diameter of PUSA particle was80-160nm, the CMC of PUSA1, PUSA2, PUSA3was50μg/mL,32μg/mL,18μg/mL respectively. With the DS of stearic acid moiety increased, the diameter and the CMC of the PUSA nanoparticles decreased.Doxorubicine (DOX), as a model drug, was loaded into the self-assembled nanoparticles of PUSA, and the higher encapsulation efficiency (84%) and drug loading content (7.79%) were achieved in PUSA3. The release of DOX in nanoparticles in vitro at pH7.4demonstrated slow sustained released over90h, 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 (1000μg/mL). The uptake efficiency of PUSA/DOX, analysized 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.