Shell-crosslinked zein nanocapsules for oral codelivery of exemestane and resveratrol in breast cancer therapy

Abstract

Aim: Oral administration of exemestane (EXM) and resveratrol (RES) for breast cancer therapy has been limited by their poor solubility and low permeability. Methods: In this study, these issues were tackled using zein nanocapsules (ZNCs) for oral EXM/RES codelivery combining drug solubilization within oily core and resistance to digestion via hydrophobic protein shell. Furthermore, higher oral stability and sustained release could be enabled by glutaraldehyde crosslinking of zein shell. Results & conclusion: EXM/RES-ZNCs showed enhanced cytotoxicity against MCF-7 and 4T1 breast cancer cells compared with free drug combination with higher selectivity to cancer cells rather than normal fibroblasts. In vivo, crosslinked EXM/RES-ZNCs markedly reduced the percentage increase of Ehrlich ascites mammary tumor volume in mice by 2.4-fold compared with free drug combination.