期刊
JOURNAL OF PHARMACY AND PHARMACOLOGY
卷 72, 期 4, 页码 496-506出版社
OXFORD UNIV PRESS
DOI: 10.1111/jphp.13223
关键词
bioavailability; cardiotoxicity; hydroxyapatite; Zein; pH-sensitive release
资金
- National Natural Science Foundation of China [51303006, 81703805]
- Provincial Natural Science Foundation of Anhui Province [KJ2018ZD031, 14080 85MH196]
- University excellent top-notch personnel training fund of Anhui Province [gxfx2017050]
Objectives Zein nanoparticles (Zein NPs) were used as a hydroxyapatite (HA) biomineralization template to generate HA/Zein NPs. Doxorubicin hydrochloride (DOX) was loaded on HA/Zein NPs (HA/Zein-DOX NPs) to improve its pH-sensitive release, bioavailability and decrease cardiotoxicity. Methods HA/Zein-DOX NPs were prepared by phase separation and biomimetic mineralization method. Particle size, polydispersity index (PDI), Zeta potential, transmission electron microscope, X-ray diffraction and Fourier-transform infrared spectroscopy of HA/Zein-DOX NPs were characterized. The nanoparticles were then evaluated in vitro and in vivo. Key findings The small PDI and high Zeta potential demonstrated that HA/Zein-DOX NPs were a stable and homogeneous dispersed system and that HA was mineralized on Zein-DOX NPs. HA/Zein-DOX NPs showed pH-sensitive release. Compared with free DOX, HA/Zein-DOX NPs increased cellular uptake which caused 7 times higher in-vitro cytotoxicity in 4T1 cells. Pharmacokinetic experiments indicated the t(1/2 beta) and AUC(0-)(t) of HA/Zein-DOX NPs were 2.73- and 3.12-fold higher than those of DOX solution, respectively. Tissue distribution exhibited HA/Zein-DOX NPs reduced heart toxicity with lower heart targeting efficiency (18.58%) than that of DOX solution (37.62%). Conclusion In this study, HA/Zein-DOX NPs represented an antitumour drug delivery system for DOX in clinical tumour therapy with improved bioavailability and decreased cardiotoxicity.
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