Diselenide-crosslinked carboxymethyl chitosan nanoparticles for doxorubicin delivery: Preparation and in vivo evaluation

In this paper, we report a simple approach to fabricate diselenide-crosslinked carboxymethyl chitosan nanoparticles (DSe-CMC NPs) for doxorubicin (DOX) delivery, with disulfide analogs (DS-CMC NPs) as control. DSCMC NPs and DSe-CMC NPs featured a spherical morphology and narrow size distribution with the average size about 200 nm. Carboxymethyl chitosan (CMC) as the starting material not only improved the biocompatibility of the nanocarriers but also enhanced physiological stability. Due to electrostatic interactions between DOX and CMC, the nanoparticles had high drug encapsulation efficiency (similar to 25 %). The nanoparticles disintegration and drug release were accelerated by the cleavage of diselenide bonds through oxidation by H2O2 or reduction by GSH. In vitro cell experiments revealed that DOX-loaded DSe-CMC NPs possessed the highest drug accumulation and cytotoxicity in tumor cells. Moreover, DOX-loaded DSe-CMC NPs performed the enhanced growth inhibition in vivo than that of DS-CMC NPs. Thus, the diselenide-crosslinked nanoparticles possess great potentials for DOX delivery.

Automated summary

In this study, diselenide-crosslinked nanoparticles were successfully fabricated for doxorubicin delivery. The nanoparticles exhibited desirable morphology and size distribution, and the starting material used improved biocompatibility and physiological stability. The high drug encapsulation efficiency of the nanoparticles was achieved through electrostatic interactions between doxorubicin and the material. In vitro and in vivo experiments demonstrated that the doxorubicin-loaded diselenide-crosslinked nanoparticles had higher drug accumulation and enhanced growth inhibition compared to the control samples.