Bilayer Nanocarriers with Protein–Acid Conjugation for Prolonged Release and Enhanced Anticancer Effects
2019
Hou, Heting | Zhang, Dong | Zeng, Jie | Zhou, Liping | Wang, Zhe | Yao, Maojin | Ren, Jiaoyan | Hu, Nan | Wang, Yi
Conventional chemotherapy, because of the high dose to keep the drug above the minimum effective concentration, possesses severe side effects and brings extra pain to patients. A controlled release drug delivery system, which is a bilayer self-assembled nanoparticle (NP) in this study, can solve this problem. Zein, a biodegradable natural protein from corn, was selected for the first layer of the drug encapsulation. The second layer was formed via the reversible ionic hydrogen bonds between zein and folic acid (FA), which was selected because of the two carboxylic acids and one amine group in its simple structure. Doxorubicin (DOX), a popular anticancer drug, was selected as the drug model to form the bilayer drug nanoencapsulation FA-NP-DOX. The in vitro controlled release profile of FA-NP-DOX was obtained. The in vivo pharmacokinetics and anticancer activity of FA-NP-DOX in tumor-xenografted animal models were also conducted. Compared to the zein nanoencapsulation of DOX (NP-DOX) and pure DOX, FA-NP-DOX showed comparable in vitro cytotoxicity but much longer in vitro controlled release time and in vivo circulation time. Both FA-NP-DOX and NP-DOX showed enhanced therapeutical efficiency in vivo than pure DOX. It is concluded that the bilayer self-assembled NP of zein and FA highly prolonged the controlled release and enhanced the therapeutic efficiency of the anticancer drug.
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