Fabrication of Polysaccharide-Stabilized Zein Nanoparticles by Flash Nanoprecipitation for Doxorubicin Sustained Release

The effective fabrication of biocompatible and robust delivery carriers is an ongoing challenge in the nano medicine for cancer treatments. Zein has proven Generally Recognized as Safe (GRAS) for clinical uses. However, its poor solubility and stability in aqueous media limits the broad applications of zein-based nanoparticles (NPs). In this study, a novel flash nanoprecipitation (FNP) was utilized to fabricate polysaccharide-stabilized zein NPs (polysaccharide/zein NPs) with small size and good stability over two weeks. The physicochemical properties of NPs were determined by the concentration and polysaccharides/zein weight ratio. FNP preparation at lower concentration (0.5 mg/mL) of polysaccharides and zein as well as the weight ratio of 1:1 led to the formation of smaller NPs with lower polydispersity. Alginate-stabilized zein NPs (AlgZ) exhibited excellent drug encapsulation efficiency (-77.9%) and loading capacity up to 16.3% when they were used as carriers for doxorubicin (DOX). Specifically, DOX-loaded AlgZ showed sustained release of DOX, which enables the significantly prolonged cancer cell-killing and inhibits the burst release of DOX, thus exhibited great potential in the sustainable delivery of hydrophobic drugs.