Key result
Pre-treatment with berberine-loaded solid lipid nanoparticles reduced doxorubicin-induced cytotoxicity in H9c2 rat cardiomyocytes from 58.91% to 40.7% (p<0.001).
Why the study?
Berberine is cardioprotective, but has low oral bioavailability and its effect on chemotherapy-induced cardiotoxicity had not been studied.
Do berberine-loaded solid lipid nanoparticles prevent doxorubicin-induced injury in H9c2 rat cardiomyocytes?
Do berberine-loaded solid lipid nanoparticles prevent doxorubicin-induced injury in H9c2 rat cardiomyocytes?
Absolute Event Rate: 40.7% vs 58.91%
p-value: p=<0.001
Berberine solid lipid nanoparticles effectively prevent doxorubicin-induced inflammation and oxidative stress in rat cardiomyocytes in vitro.
Ber-SLNs reduce Dox cytotoxicity in rat cardiomyocytes; hypothesis-generating for cardioprotection, requiring in vivo confirmation before clinical consideration.
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.
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Gupta et al. (2022) studied Doxorubicin-induced cardiotoxicity. Berberine-loaded solid lipid nanoparticles (Ber-SLNs) vs. Doxorubicin alone was evaluated on Percentage cytotoxicity calculated from LDH release (p=<0.001). Pre-treatment with berberine-loaded solid lipid nanoparticles reduced doxorubicin-induced cytotoxicity in H9c2 rat cardiomyocytes from 58.91% to 40.7% (p<0.001).
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