Cancer Nanotechnology Research Laboratory (CNRL), Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt.
Department of Industrial Pharmacy, Faculty of Pharmacy, Alexandria University, Alexandria 21521, Egypt.
Nanomedicine (Lond). 2017 Dec;12(24):2785-2805. doi: 10.2217/nnm-2017-0247. Epub 2017 Nov 2.
Oral administration of exemestane (EXM) and resveratrol (RES) for breast cancer therapy has been limited by their poor solubility and low permeability.
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.
阿那曲唑（EXM）和白藜芦醇（RES）的口服给药在用于乳腺癌治疗时受到其较差的溶解度和低渗透性的限制。
在这项研究中，通过使用玉米醇溶蛋白纳米胶囊（ZNC）来解决这些问题，将药物溶解在油核内，并通过疏水性蛋白质壳来抵抗消化，从而实现了 EXM/RES 的口服共递药。此外，通过戊二醛交联玉米醇溶蛋白壳，可以实现更高的口服稳定性和持续释放。
EXM/RES-ZNC 对 MCF-7 和 4T1 乳腺癌细胞的细胞毒性明显高于游离药物组合，对癌细胞的选择性更高，而对正常成纤维细胞的选择性较低。在体内，与游离药物组合相比，交联的 EXM/RES-ZNC 使艾氏腹水癌乳腺肿瘤体积的百分比增加减少了 2.4 倍。
