Trastuzumab-conjugated nanoparticles composed of poly(butylene adipate-co-butylene terephthalate) prepared by electrospraying technique for targeted delivery of docetaxel.

Abstract

Human epidermal growth factor receptor 2 (HER-2) is overexpressed in 20-30% of human breast cancers, associated with poor prognosis and tumour aggression. The aim of this study was the production of trastuzumab-targeted Ecoflex nanoparticles (NPs) loaded with docetaxel and in vitro evaluation of their cytotoxicity and cellular uptake. The NPs were manufactured by electrospraying and characterised regarding size, zeta potential, drug loading, and release behaviour. Then their cytotoxicity was evaluated by MTT assay against an HER-2-positive cell line, BT-474, and an HER-2-negative cell line, MDA-MB-468. The cellular uptake was studied by flow cytometry and fluorescent microscope. The particle size of NPs was in an appropriate range, with relatively high drug entrapment and acceptable release efficiency. The results showed no cytotoxicity for the polymer, but the significant increment of cytotoxicity was observed by treatment with docetaxel-loaded NPs in both HER-2-positive and HER-2-negative cell lines, in comparison with the free drug. The trastuzumab-targeted NPs also significantly enhanced cytotoxicity against BT-474 cells, compared with non-targeted NPs.