Abstract
This study proposes a new zein nanoparticle (ZP) encapsulated 5-fluorouracil (5-FU) that target liver through intravenous delivery. The ZPs were prepared by phase separation process and optimized using uniform experimental design. The physical properties, in vitro drug release and stability of optimal drug-loaded ZPs were studied. The biodistribution and the target efficiency of the particles were investigated in a mouse model. The highest drug loading was obtained using zein: 5-FU, 3:1 (v/v); zein concentration, 12.5mg/ml, pH 9.18, mixing time, 3h and ethanol concentration, 40%. The encapsulation efficiency and the drug loading were 60.7±1.74 and 9.17±0.11 respectively. The size of ZPs and zeta potential were 114.9±59.4nm and −45±0.3mV respectively. Differential scanning calorimetry (DSC) demonstrated that the drug was encapsulated within the ZPs. A sustained release profile of 5-FU was observed from ZPs. The more stable storage condition of ZPs was at a temperature of 4°C. In vivo, ZPs was mostly accumulated in liver following intravenous injection, and the targeting efficiency increased 31.33%. The relative uptake rate of liver was 2.79. Also, nano-sized ZPs were beneficial for prolonged blood residence (7.2-fold increase). These demonstrated that the drug-loaded ZPs could be efficiently targeted at the liver by intravenous delivery.
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