Targeted delivery of doxorubicin to liver used a novel biotinylated β-cyclodextrin grafted pullulan nanocarrier

Abstract

A series of biotinylated β-cyclodextrin grafted pullulan (Bio-CDPu) for liver-specific drug delivery were synthesized and characterized by Fourier transform infrared (FTIR) and hydrogen nuclear magnetic resonance (1H NMR) spectroscopy, and then their self-assembled spherical nanoparticles (NPs) with 110–200 nm diameter were prepared. Doxorubicin (DOX) was selected as an anti-cancer model drug to prepare the drug-loaded NPs, and the drug loading efficiency (LE%) and loading content (LC%) were determined. The drug release behavior in vitro of DOX/Bio-CDPu NPs exhibited sustained release. The results of methyl thiazolyl tetrazolium (MTT) assays, confocal laser scanning microscopy (CLSM) observations and flow cytometric (FCM) analysis indicated that the designed Bio-CDPu nanocarriers showed good cytocompatibility with Bel-7404 cells and high cellular uptake. Due to their rich biotin /or pullulan ligands, Bio-CDPu NPs could promote DOX to enter Bel-7404 cells and inhibit the tumor cell growth. After intravenous injection to rats, DOX/Bio-CDPu NPs solution exhibited increased area under the curve (AUC) and prolonged half life time (t1/2), meanwhile, the drug concentration in the liver was significantly increased, and the cardio-renal toxicity was reduced. Furthermore, DOX/Bio-CDPu NPs exhibited a better anti-tumor therapeutic effect on tumor-bearing mice. Therefore, Bio-CDPu NPs can be chosen as a potential high-efficiency liver targeted carrier.