Preparation and in vitro evaluation of lactobionic acid modified polyamide-amine dendrimer grafted resveratrol nanoparticles / 中草药

ABSTRACT

Objective: To prepare resveratrol (Res) nanoparticles grafted with polyamide-amine dendrimer (PAMAM) modified by lactose acid (LA) and evaluate them in vitro. Methods: After partial carboxylation of G3.0 PAMAM terminal (PAMAM-COOH) which synthesized by divergence method. Res was bonded through esterification reaction and LA was grafted on the surface of the carrier through amidation reaction. Nuclear magnetic resonance (1H-NMR) and infrared spectroscopy (IR) were used for characterization. La-PAMAM-Res/Res nanoparticles were prepared by physical encapsulation using LA-PAMAM-Res and Res, and the encapsulation rate was detected by dialysis method. The drug load of the two kinds of nanoparticles was detected by high performance liquid chromatography (HPLC), the particle size was investigated by laser particle size analysis method, the drug release performance in vitro was determined by dialysis method, and the biosafety was evaluated by hemolytic experiment. The cytotoxicity and anticancer activity of PAMAM, PAMAM-COOH, Res, LA-PAMAM-Res and LA-PAMAM-Res/Res were investigated by MTT assay. Results: LA- PAMAM-Res and La-PAMAM-Res/Res nanoparticles were prepared. The encapsulation rate of LA-PAMAM-Res/Res was (75.1 ±2.2) %, the drug loading rates of LA-PAMAM-Res and LA-PAMAM-Res/Res were (7.2 ± 0.9) % and (18.4 ± 1.1) %, respectively. The particle size was (126.3 ± 3.4) nm and (251.0 ± 15.7) nm, respectively. After 72 h, the drug release in vitro was (23.83 ± 0.43)% and (35.28 ± 0.72)%, respectively. The hemolysis rate of both nanoparticles was less than 5%, and the carrier PAMAM-COOH showed less cytotoxicity than PAMAM, and both LA-PAMAM-Res and LA-PAMAM-Res/Res maintained anti-tumor proliferative activity. Conclusion: LA-PAMAM-Res and LA-PAMAM-Res/Res nanoparticles with sustained drug release, good biocompatibility, low cytotoxicity and anticancer activity were prepared, and LA-PAMAM-Res/Res increased the drug load of Res.