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Abstract
Background:
Doxorubicin (DOX), a broad-spectrum chemotherapy drug, is clinically employed to treat cancers especially for breast cancer and lung cancer. But its clinical applications are limited by the dose-dependent cardiac toxicity. Resveratrol (Res), a polyphenolic antitoxin, has been proved to be capable of improving the cardiomyocyte calcium cycling by up-regulating SIRT-1-mediated deacetylation to inhibit DOX-induced cardiotoxicity.
Purpose:
The objective of this study was to develop a solid lipid nanoparticle (SLN) loaded with Res to trigger inhibition of DOX-induced cardiotoxicity.
Methods:
Res-SLN was prepared by emulsification-diffusion method followed by sonication and optimized using central composite design/response surface method. The Res-SLN was further evaluated by dynamic light scattering, transmission electron microscopy for morphology and high performance liquid chromatography for drug loading and release profile. And the Res distribution in vivo was determined on rats while the effect of inhibit DOX-induced cardiotoxicity was investigated on mice.
Results:
Res-SLN with homogeneous particle size of 271.13 nm was successfully formulated and optimized. The prepared Res-SLN showed stable under storage and sustained release profile, improving the poor solubility of Res. Heart rate, ejection fractions and fractional shortening of Res-SLN treating mice were found higher than those on mice with cardiac toxicity induced by single high-dose intraperitoneal injection of DOX. And the degree of myocardial ultrastructural lesions on mice was also observed.
Conclusion:
Res-SLN has a certain therapeutic effect for protecting the myocardium and reducing DOX-induced cardiotoxicity in mice.
Acknowledgments
The work was supported by grants from Shanghai Committee of Science and Technology (17401902300 and 18401931400), the Program of Shanghai Academic/Technology Research Leader (18XD1403700), Shanghai Three-year Action Plan for the Development of Traditional Chinese Medicine [ZY(2018-2020)-CCCX-2001-04] and the National Scientific and Technological Major Special Project of China (2018ZX09201008-002).
Abbreviation list
Dox, doxorubicin; Res, resveratrol; SLN, solid lipid nanoparticles; GMS, glycerol monostearate; TEM, transmission electron microscopy; IS, internal standard; UPLC, ultra-high performance liquid chromatography; HR, heart rate; EF, ejection fractions; FS, fractional shortening.
Disclosure
The authors report no conflicts of interest in this work.