Disulfiram-Loaded Nanoparticles Inhibit Long-Term Proliferation on Preadipocytes

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

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 macroph

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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