Preparation, characterization and preliminary pharmacokinetic study of pH‐sensitive Hydroxyapatite/Zein nano‐drug delivery system for doxorubicin hydrochloride. (24th January 2020)

• Record Type: Journal Article
• Authors: Zha, Liqiong; Wang, Beilei; Qian, Jiajia; Fletcher, Brock; Zhang, Caiyun; Dong, Qiannian; Chen, Weidong; Hong, Lufeng
• Is Part Of: Journal of pharmacy and pharmacology. Volume 72:Number 4(2020)
• Page Start: 496
• Page End: 506
• Publication Date: 2020-01-24
• Subjects: bioavailability -- cardiotoxicity -- hydroxyapatite/Zein -- pH‐sensitive release; Pharmacy -- Periodicals; Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/jphp.13223
• Languages: English
• ISSNs: 0022-3573

Abstract

Abstract: 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 1/2β and AUC0– 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.