Preparaton of selenium nanoparticles stabilized by pullulan and derivatives

Abstract

The inorganic/organic selenium nanoparticles (SeNPs)/pullulan derivative hybrid material was obtained using a simple and green strategy. The chemical structure of pullulan, folic acid decorated cationic pullulan (FA-CP) was designed for stabilizing SeNPs. The SeNPs stabilized by FA-CP were observed after the addition of a cysteine hydrochloride solution into the solution mixture of Na2SeO3 and FA-CP. The results suggested that the concentrations of cysteine and stabilizer were the key factors to control the shape and morphology of SeNPs. The spherical SeNP/FA-CP was found in ratio of Na2SeO3 to cysteine was 1:1. It exhibited low toxicity against normal cells while higher toxicity was showed in human cancer cell lines Moreover, the enhancement of cellular uptake of spherical SeNPs/FA-CP was performed comparing with SeNPs stabilized by unmodified pullulan. The unexpected formation of flower-like structure was performed when using 1:2 molar ratio of Na2SeO3 to cysteine. The formation mechanism of the microflowers was tentatively identified as anisotropic hierarchical growth. The microflowers exhibited effective drug adsorption for doxorubicin which was three times higher than that for the doxorubicin loaded spherical SeNPs/FA-CP and showed more potent activity against cancer cells while showing less toxicity against normal cells. The data demonstrated that the microflower SeNPs/FA-CP could be a candidate anticancer drug template in drug delivery systems. To enhance drug loading capacity and create universal drug loading template for drug delivery application, the ß-cyclodextrin was conjugated on FA-CP (CD-FA-CP) and use for stabilization of SeNPs (SeNPs/CD-FA-CP). The maximum loading capacity of doxorubicin of the microflower SeNPs/CD-FA-CP was four times higher than the capacity of microflower stabilized by FA-CP. In addition, others guest molecules; curcimin and methylene blue could be loaded into SeNPs/CD-FA-CP hybrid microflower. These finding showed that the SeNPs/CD-FA-CP microflowers can be used as universal template for any gest molecules especially hydrophobic drugs. Thus, this work presents an alternative way for using SeNPs/pullulan derivative as a carrier-based drug delivery system for cancer treatment.