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Open AccessArticle

Liposomes Co-Encapsulating Cisplatin/Mifepristone Improve the Effect on Cervical Cancer: In Vitro and In Vivo Assessment

1
Laboratorio de Farmacologia, Subdirección de Investigación Básica, Instituto Nacional de Cancerología, Cd. México 14080, Mexico
2
Posgrado en Ciencias Biológicas, Universidad Nacional Autónoma de México, Coyacán, Cd. México 04510, Mexico
3
Unidad de Investigación Biomédica en Cáncer INCan-UNAM, Instituto Nacional de Cancerología, Cd. México 14080, Mexico
4
Instituto de Física, Universidad Nacional Autónoma de México, Coyoacán, Cd. México 04510, Mexico
*
Author to whom correspondence should be addressed.
Pharmaceutics 2020, 12(9), 897; https://doi.org/10.3390/pharmaceutics12090897
Received: 11 August 2020 / Revised: 12 September 2020 / Accepted: 16 September 2020 / Published: 22 September 2020
(This article belongs to the Special Issue New Formulations for Cancer Therapy)
Cervical cancer is usually diagnosed in the later stages despite many campaigns for early detection and continues to be a major public health problem. The standard treatment is cisplatin-based chemotherapy plus radiotherapy, but patient response is far from ideal. In the research for new drugs that enhance the activity of cisplatin, different therapeutic agents have been tested, among them the antiprogestin mifepristone. Nevertheless, the efficacy of cisplatin is limited by its low specificity for tumor tissue, which causes severe side effects. Additionally, cervical tumors often become drug resistant. These problems could possibly be addressed by the use of liposome nanoparticles to encapsulate drugs and deliver them to the target. The aim of this study was to prepare liposome nanoparticles that co-encapsulate cisplatin and mifepristone, evaluate their cytotoxicity against HeLa cells and in vivo with subcutaneous inoculations of xenografts in nu/nu mice, and examine some plausible mechanisms of action. The liposomes were elaborated by the reverse-phase method and characterized by physicochemical tests. The nanoparticles had a mean particle size of 109 ± 5.4 nm and a Zeta potential of −38.7 ± 1.2 mV, the latter parameter indicating a stable formulation. These drug-loaded liposomes significantly decreased cell viability in vitro and tumor size in vivo, without generating systemic toxicity in the animals. There was evidence of cell cycle arrest and increased apoptosis. The promising results with the co-encapsulation of cisplatin/mifepristone warrant further research. View Full-Text
Keywords: cervical cancer; cisplatin; co-encapsulation; drug combination; liposomes; mifepristone; synergism cervical cancer; cisplatin; co-encapsulation; drug combination; liposomes; mifepristone; synergism
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MDPI and ACS Style

Ledezma-Gallegos, F.; Jurado, R.; Mir, R.; Medina, L.A.; Mondragon-Fuentes, L.; Garcia-Lopez, P. Liposomes Co-Encapsulating Cisplatin/Mifepristone Improve the Effect on Cervical Cancer: In Vitro and In Vivo Assessment. Pharmaceutics 2020, 12, 897.

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