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Disulfiram-Loaded Nanoparticles Inhibit Long-Term Proliferation on Preadipocytes.

Helen Yarimet Lorenzo-Anota1,2, José María Gómez-Cantú2, Eduardo Vázquez-Garza1

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International Journal of Nanomedicine
|December 16, 2024
PubMed
Summary

Poly-ε-caprolactone (PCL) nanoparticles effectively deliver disulfiram (DSF) to adipose tissue. This sustained release shows selective toxicity to preadipocytes, offering a promising alternative for treating obesity-related conditions.

Keywords:
adipocyteadipose tissuecytotoxicitydrug loadingobesitypolymeric nanoparticles

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Area of Science:

  • Biomaterials Science
  • Pharmacology
  • Cell Biology

Background:

  • Disulfiram (DSF) demonstrates potential in reducing insulin resistance and weight gain.
  • The instability of DSF limits its clinical application, necessitating a stable delivery system.
  • Adipose tissue's role in metabolic diseases requires targeted therapeutic strategies.

Purpose of the Study:

  • To develop and optimize poly-ε-caprolactone (PCL) nanoparticles for sustained disulfiram (DSF) delivery to adipose tissue.
  • To evaluate the in vitro effects of DSF-loaded PCL nanoparticles on adipose tissue cells.
  • To assess the safety and efficacy of nanoencapsulated DSF compared to free DSF.

Main Methods:

  • Poly-ε-caprolactone (PCL) nanoparticles loaded with DSF were synthesized using the nanoprecipitation method.
  • Optimization involved varying solvent mixtures and PCL:DSF ratios, with the best condition identified as an acetone/dichloromethane mixture and a 2:1 ratio.
  • NPs toxicity was assessed on preadipocytes, white-like adipocytes, and macrophages by evaluating cell viability, internalization, and apoptosis.

Main Results:

  • Optimized PCL-DSF NPs exhibited spherical morphology, a particle size of ~203 nm, and sustained drug release over 96 hours.
  • NPs were internalized by adipose cells without affecting viability in macrophages and white-like adipocytes.
  • Preadipocytes showed reduced viability, mitochondrial damage, and apoptosis upon exposure to NPs, similar to free DSF but with potentially milder effects.

Conclusions:

  • PCL nanoparticles provide a viable carrier for sustained DSF delivery to adipose tissue.
  • Nanoencapsulation of DSF demonstrates selective cytotoxicity towards preadipocytes, with potentially reduced side effects compared to free DSF.
  • These findings suggest PCL-DSF NPs as a promising therapeutic alternative for adipose tissue-targeted treatments.