Development of polyethyleneimine cross-linked fucoidan nanoparticles as delivery systems for improved anticancer efficiency of cytarabine in breast adenocarcinoma cell lines†

Abstract

Cytarabine, generally used for the treatment of haematological malignancies, has minimal activity in solid tumours. The present work focuses on the evaluation of the cytotoxic efficiency of cytarabine in MCF-7 cell lines with the aid of fucoidan nanoparticles as drug delivery systems. Polyethyleneimine (PEI) crosslinked fucoidan nanoparticles were synthesised by polyelectrolyte complexation and were characterised by FTIR and ¹H NMR. TEM analysis revealed cytarabine-loaded fucoidan nanoparticles (CFNPs) with a size of less than 40 nm. In vitro release kinetics studies showed that the release of cytarabine (82.17 ± 1.24%) from CFNPs was higher at pH 6.4. Molecular simulation studies revealed that fucoidan–cytarabine binding is mainly facilitated by hydrogen bonds. Internalisation of fucoidan nanoparticles by MCF-7 cells was tracked using the fluorophore, SQ 650. Cell viability studies showed improved cytotoxicity in CFNP-treated MCF-7 cell lines compared to free cytarabine. Quantitative real-time PCR showed upregulation of the expression of apoptotic genes, bax, cyt c and cas 9 in cells treated with CFNPs. Flow cytometry using Annexin V/PI displayed an increased percentage of apoptotic cells on treatment with CFNPs compared to cytarabine alone. The result of this study shows that the cytotoxic efficiency of cytarabine in MCF-7 cells can be enhanced using fucoidan nanoparticles as delivery systems.