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

Autor:	Lorenzo-Anota HY; Tecnologico de Monterrey, Institute for Obesity Research, Monterrey, México.; Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, México., Gómez-Cantú JM; Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, México., Vázquez-Garza E; Tecnologico de Monterrey, Institute for Obesity Research, Monterrey, México., Bernal-Ramirez J; Tecnologico de Monterrey, Institute for Obesity Research, Monterrey, México., Chapoy-Villanueva H; Tecnologico de Monterrey, Institute for Obesity Research, Monterrey, México.; Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, México., Mayolo-Deloisa K; Tecnologico de Monterrey, Institute for Obesity Research, Monterrey, México.; Tecnologico de Monterrey, Escuela de Ingeniería y Ciencias, Centro de Biotecnología-FEMSA, Monterrey, México., Benavides J; Tecnologico de Monterrey, Institute for Obesity Research, Monterrey, México.; Tecnologico de Monterrey, Escuela de Ingeniería y Ciencias, Centro de Biotecnología-FEMSA, Monterrey, México., Rito-Palomares M; Tecnologico de Monterrey, Institute for Obesity Research, Monterrey, México.; Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, México., Lozano O; Tecnologico de Monterrey, Institute for Obesity Research, Monterrey, México.; Tecnologico de Monterrey, Escuela de Medicina y Ciencias de la Salud, Monterrey, México.
Jazyk:	angličtina
Zdroj:	International journal of nanomedicine [Int J Nanomedicine] 2024 Dec 10; Vol. 19, pp. 13301-13318. Date of Electronic Publication: 2024 Dec 10 (Print Publication: 2024).
DOI:	10.2147/IJN.S467909
Abstrakt:	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. Competing Interests: The authors declare no conflict of interest. (© 2024 Lorenzo-Anota et al.)
Databáze:	MEDLINE
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