ArticleInternational journal of nanomedicine2024
Disulfiram-Loaded Nanoparticles Inhibit Long-Term Proliferation on Preadipocytes.
Article in International journal of nanomedicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
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9 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Introduction: Disulfiram (DSF) reduces insulin resistance and weight gain in obese mice. However, the effect on adipose tissue is unexplored due to their high instability under physiological conditions, limiting clinical applications. Thus, it is meaningful to develop a DSF carrier for sustained release to adipose tissue. We optimized the synthesis of poly-ε-caprolactone (PCL) nanoparticles (NPs) loaded with DSF and analyzed their effect on adipose tissue cells in vitro. Methods: The NPs were synthesized by nanoprecipitation method, varying its solvent, either acetone or acetone/dichloromethane (60:40) (v/v), and ratio PCL:DSF (w/w) 1:2, 1:1, 2:1 and, 1:0; finding the best condition was obtained with acetone/dichloromethane solvent mixture and 2:1 PCL:DSF. Then, NPs toxicity was analyzed on adipose cells (preadipocytes, white-like adipocytes, and macrophages) assessing association and internalization, cell viability, and cell death mechanism. Results: NPs were spherical with a particle size distribution of 203.2 ± 29.33 nm, a ζ-potential of -20.7 ± 4.58 mV, a PDI of 0.296 ± 0.084, and a physical drug loading of 18.6 ± 5.80%. Sustained release was observed from 0.5 h (10.94 ± 2.38%) up to 96 h (91.20 ± 6.03%) under physiological conditions. NPs internalize into macrophages, white-like adipocytes and preadipocytes without modifying cell viability on white-like adipocytes and macrophages. Preadipocytes reduce cell viability, inducing mitochondrial damage, increased mitochondrial reactive oxygen species production and loss of mitochondrial membrane potential, leading to effector caspases 3/7 cleaved, resulting in apoptosis. Finally, long-term proliferation inhibition was observed, highlighting the bioequivalent effect of PCL-DSF NPs compared to free DSF. Conclusion: Our data demonstrated the biological interaction of PCL NPs with adipose cells in vitro. The selective cytotoxicity of DSF towards preadipocytes resulted in milder effects when it was delivered nanoencapsulated compared to the free drug. These results suggest promising pharmacological alternatives for DSF long-term delivery on adipose tissue.
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