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

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...

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Autores principales: Ledezma-Gallegos, Fabricio, Jurado, Rafael, Mir, Roser, Medina, Luis Alberto, Mondragon-Fuentes, Laura, Garcia-Lopez, Patricia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558205/
https://www.ncbi.nlm.nih.gov/pubmed/32971785
http://dx.doi.org/10.3390/pharmaceutics12090897
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author Ledezma-Gallegos, Fabricio
Jurado, Rafael
Mir, Roser
Medina, Luis Alberto
Mondragon-Fuentes, Laura
Garcia-Lopez, Patricia
author_facet Ledezma-Gallegos, Fabricio
Jurado, Rafael
Mir, Roser
Medina, Luis Alberto
Mondragon-Fuentes, Laura
Garcia-Lopez, Patricia
author_sort Ledezma-Gallegos, Fabricio
collection PubMed
description 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.
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spelling pubmed-75582052020-10-29 Liposomes Co-Encapsulating Cisplatin/Mifepristone Improve the Effect on Cervical Cancer: In Vitro and In Vivo Assessment Ledezma-Gallegos, Fabricio Jurado, Rafael Mir, Roser Medina, Luis Alberto Mondragon-Fuentes, Laura Garcia-Lopez, Patricia Pharmaceutics Article 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. MDPI 2020-09-22 /pmc/articles/PMC7558205/ /pubmed/32971785 http://dx.doi.org/10.3390/pharmaceutics12090897 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ledezma-Gallegos, Fabricio
Jurado, Rafael
Mir, Roser
Medina, Luis Alberto
Mondragon-Fuentes, Laura
Garcia-Lopez, Patricia
Liposomes Co-Encapsulating Cisplatin/Mifepristone Improve the Effect on Cervical Cancer: In Vitro and In Vivo Assessment
title Liposomes Co-Encapsulating Cisplatin/Mifepristone Improve the Effect on Cervical Cancer: In Vitro and In Vivo Assessment
title_full Liposomes Co-Encapsulating Cisplatin/Mifepristone Improve the Effect on Cervical Cancer: In Vitro and In Vivo Assessment
title_fullStr Liposomes Co-Encapsulating Cisplatin/Mifepristone Improve the Effect on Cervical Cancer: In Vitro and In Vivo Assessment
title_full_unstemmed Liposomes Co-Encapsulating Cisplatin/Mifepristone Improve the Effect on Cervical Cancer: In Vitro and In Vivo Assessment
title_short Liposomes Co-Encapsulating Cisplatin/Mifepristone Improve the Effect on Cervical Cancer: In Vitro and In Vivo Assessment
title_sort liposomes co-encapsulating cisplatin/mifepristone improve the effect on cervical cancer: in vitro and in vivo assessment
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7558205/
https://www.ncbi.nlm.nih.gov/pubmed/32971785
http://dx.doi.org/10.3390/pharmaceutics12090897
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