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Combinatorial Chemistry & High Throughput Screening

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ISSN (Print): 1386-2073
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Research Article

Solid Lipid Nanoformulation of Berberine Attenuates Doxorubicin Triggered in vitro Inflammation in H9c2 Rat Cardiomyocytes

Author(s): Shalini Rawal, Pooja Gupta*, Priyanka Bhatnagar, Harlokesh Narayan Yadav and Amit Kumar Dinda

Volume 25, Issue 10, 2022

Published on: 27 July, 2022

Page: [1695 - 1706] Pages: 12

DOI: 10.2174/1386207325666220617113744

Price: $65

Abstract

Aim: The aim of this study was to evaluate the efficacy of solid lipid nanoparticles of berberine against doxorubicin-induced cardiotoxicity.

Background: Berberine (Ber) is cardioprotective, but its oral bioavailability is low, and its effect on chemotherapy-induced cardiotoxicity has not been studied.

Objective: Solid lipid nanoparticles (SLNs) of berberine chloride were prepared, characterized and evaluated in vitro against doxorubicin-induced cardiomyocyte injury.

Methods: Berberine-loaded SLNs (Ber-SLNs) were synthesized using the water-in-oil microemulsion technique with tripalmitin, Tween 80 and poloxamer 407. Ber-SLNs were evaluated for preventive effect against toxicity of doxorubicin in H9c2 cells. The culture was pre-treated (24 h) with Ber (10 μM) and Ber-SLNs (1 and 10 μM), and 1 μM of doxorubicin (Dox) was added for 3 h. The cell viability assay (MTT (3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide) and LDH (Lactate dehydrogenase)), levels of Creatine kinase-MB (CK-MB), Nitrite, MDA (Malondialdehyde), ROS (Reactive oxygen species) generation, and apoptotic DNA (Deoxyribonucleic acid) content were assessed.

Results: Ber-SLNs had a mean particle size of 13.12±1.188 nm, the zeta potential of -1.05 ± 0.08 mV, poly-dispersity index (PDI) of 0.317 ± 0.05 and entrapment efficiency of 50 ± 4.8%. Cell viability was 81 ± 0.17% for Ber-SLNs (10 μM) and 73.22 ± 0.83% for Ber (10 μM) treated cells in the MTT assay. Percentage cytotoxicity calculated from LDH release was 58.91 ± 0.54% after Dox, 40.3 ± 1.3% with Ber (10 μM) and 40.7 ± 1.3% with Ber-SLNs (1 μM) (p<0.001). Inflammation and oxidative stress markers were lower with Ber and Ber-SLNs. Attenuation of ROS generation and apoptosis of cardiomyocytes were noted on fluorescence microscopy.

Conclusion: Ber SLNs effectively prevented doxorubicin-induced inflammation and oxidative stress in rat cardiomyocytes. The results demonstrate that microemulsion is a simple and costeffective technique to prepare Ber-SLNs, and may be considered as a drug delivery vehicle for berberine.

Keywords: Chemotherapy-induced cardiotoxicity, berberine, doxorubicin, H9c2 cells, microemulsion, solid lipid nanoparticles.

Graphical Abstract
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