Key result
HA/Zein-DOX NPs improved pharmacokinetics and reduced heart targeting efficiency compared to DOX solution (18.58% vs 37.62%), indicating decreased cardiotoxicity.
Why the study?
To develop hydroxyapatite/zein nanoparticles loaded with doxorubicin hydrochloride to improve its pH-sensitive release and bioavailability while decreasing cardiotoxicity.
Does a pH-sensitive Hydroxyapatite/Zein nano-drug delivery system for doxorubicin improve bioavailability and decrease cardiotoxicity compared to free doxorubicin in preclinical models?
Does a pH-sensitive Hydroxyapatite/Zein nano-drug delivery system for doxorubicin improve bioavailability and decrease cardiotoxicity compared to free doxorubicin in preclinical models?
Absolute Event Rate: 18.58% vs 37.62%
A novel hydroxyapatite/zein nanoparticle delivery system for doxorubicin improves drug bioavailability and reduces cardiac tissue distribution in preclinical models, suggesting a potential strategy to mitigate doxorubicin-induced cardiotoxicity.
HA/Zein-DOX NPs may lower doxorubicin cardiotoxicity in animals; leaves open clinical translation and human efficacy.
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 t1/2β 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.
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Zha et al. (2020) studied Tumour. HA/Zein-DOX NPs vs. DOX solution was evaluated on Heart targeting efficiency. HA/Zein-DOX NPs improved pharmacokinetics and reduced heart targeting efficiency compared to DOX solution (18.58% vs 37.62%), indicating decreased cardiotoxicity.
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