Antioxidants have potentials to treat
hypoxia-mediated oxidative stress related diseases. However, their therapeutic efficacy is restricted due to its poor cellular uptake efficiency and poor cell membrane permeability. To resolve these issues, we prepare the hydroxyethylated
chitosan nanoparticles as
drug carriers for the delivery of 6-hydroxy-2, 5, 7, 8-tetramethylchroman-2-carboxylic
acid (
Trolox), which was considered as a model compound. The experiment on cellular uptake and subcellular localization of
Trolox-loaded
chitosan nanoparticles (
Trolox-CSNPs) indicate that
Trolox-CSNPs enter the cells via the caveolae-mediated endocytosis pathway and traffic with endosomes. Furthermore, compared with
Trolox,
Trolox-CSNPs exert a higher protective effect against the
hypoxia-mediated oxidative stress. Molecular basis of apoptosis study reveals that
Trolox-CSNPs can directly block the mitochondria dependent apoptotic pathway through up-regulation of Bcl-2 expression and inhibiting the activation of Bax,
Caspase-3 expression. In conclusion, the hydroxyethylated
chitosan is a promising
drug nanocarrier to deliver
antioxidants for the treatment of
hypoxia-mediated disease. From the clinical editor:
Antioxidants are potentially beneficial in oxidative stress-related diseases, although cellular uptake of most
antioxidants is suboptimal. In this study, hydroxyethylated
chitosan nanoparticles are demonstrated as promising
drug carriers in a
Trolox-model system.