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Co-Encapsulation of Simvastatin and Doxorubicin into pH-Sensitive Liposomes Enhances Antitumoral Activity in Breast Cancer Cell Lines

Doxorubicin (DOX) is a potent chemotherapeutic drug used as the first line in breast cancer treatment; however, cardiotoxicity is the main drawback of the therapy. Preclinical studies evidenced that the association of simvastatin (SIM) with DOX leads to a better prognosis with reduced side effects a...

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Autores principales: Duarte, Jaqueline Aparecida, Gomes, Eliza Rocha, De Barros, André Luis Branco, Leite, Elaine Amaral
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9960841/
https://www.ncbi.nlm.nih.gov/pubmed/36839690
http://dx.doi.org/10.3390/pharmaceutics15020369
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author Duarte, Jaqueline Aparecida
Gomes, Eliza Rocha
De Barros, André Luis Branco
Leite, Elaine Amaral
author_facet Duarte, Jaqueline Aparecida
Gomes, Eliza Rocha
De Barros, André Luis Branco
Leite, Elaine Amaral
author_sort Duarte, Jaqueline Aparecida
collection PubMed
description Doxorubicin (DOX) is a potent chemotherapeutic drug used as the first line in breast cancer treatment; however, cardiotoxicity is the main drawback of the therapy. Preclinical studies evidenced that the association of simvastatin (SIM) with DOX leads to a better prognosis with reduced side effects and deaths. In this work, a novel pH-sensitive liposomal formulation capable of co-encapsulating DOX and SIM at different molar ratios was investigated for its potential in breast tumor treatment. Studies on physicochemical characterization of the liposomal formulations were carried out. The cytotoxic effects of DOX, SIM, and their combinations at different molar ratios (1:1; 1:2 and 2:1), free or co-encapsulated into pH-sensitive liposomes, were evaluated against three human breast cancer cell lines (MDA-MB-231, MCF-7, and SK-BR-3). Experimental protocols included cell viability, combination index, nuclear morphological changes, and migration capacity. The formulations showed a mean diameter of less than 200 nm, with a polydispersity index lower than 0.3. The encapsulation content was ~100% and ~70% for DOX and SIM, respectively. A more pronounced inhibitory effect on breast cancer cell lines was observed at a DOX:SIM molar ratio of 2:1 in both free and encapsulated drugs. Furthermore, the 2:1 ratio showed synergistic combination rates for all concentrations of cell inhibition analyzed (50, 75, and 90%). The results demonstrated the promising potential of the co-encapsulated liposome for breast tumor treatment.
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spelling pubmed-99608412023-02-26 Co-Encapsulation of Simvastatin and Doxorubicin into pH-Sensitive Liposomes Enhances Antitumoral Activity in Breast Cancer Cell Lines Duarte, Jaqueline Aparecida Gomes, Eliza Rocha De Barros, André Luis Branco Leite, Elaine Amaral Pharmaceutics Article Doxorubicin (DOX) is a potent chemotherapeutic drug used as the first line in breast cancer treatment; however, cardiotoxicity is the main drawback of the therapy. Preclinical studies evidenced that the association of simvastatin (SIM) with DOX leads to a better prognosis with reduced side effects and deaths. In this work, a novel pH-sensitive liposomal formulation capable of co-encapsulating DOX and SIM at different molar ratios was investigated for its potential in breast tumor treatment. Studies on physicochemical characterization of the liposomal formulations were carried out. The cytotoxic effects of DOX, SIM, and their combinations at different molar ratios (1:1; 1:2 and 2:1), free or co-encapsulated into pH-sensitive liposomes, were evaluated against three human breast cancer cell lines (MDA-MB-231, MCF-7, and SK-BR-3). Experimental protocols included cell viability, combination index, nuclear morphological changes, and migration capacity. The formulations showed a mean diameter of less than 200 nm, with a polydispersity index lower than 0.3. The encapsulation content was ~100% and ~70% for DOX and SIM, respectively. A more pronounced inhibitory effect on breast cancer cell lines was observed at a DOX:SIM molar ratio of 2:1 in both free and encapsulated drugs. Furthermore, the 2:1 ratio showed synergistic combination rates for all concentrations of cell inhibition analyzed (50, 75, and 90%). The results demonstrated the promising potential of the co-encapsulated liposome for breast tumor treatment. MDPI 2023-01-21 /pmc/articles/PMC9960841/ /pubmed/36839690 http://dx.doi.org/10.3390/pharmaceutics15020369 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Duarte, Jaqueline Aparecida
Gomes, Eliza Rocha
De Barros, André Luis Branco
Leite, Elaine Amaral
Co-Encapsulation of Simvastatin and Doxorubicin into pH-Sensitive Liposomes Enhances Antitumoral Activity in Breast Cancer Cell Lines
title Co-Encapsulation of Simvastatin and Doxorubicin into pH-Sensitive Liposomes Enhances Antitumoral Activity in Breast Cancer Cell Lines
title_full Co-Encapsulation of Simvastatin and Doxorubicin into pH-Sensitive Liposomes Enhances Antitumoral Activity in Breast Cancer Cell Lines
title_fullStr Co-Encapsulation of Simvastatin and Doxorubicin into pH-Sensitive Liposomes Enhances Antitumoral Activity in Breast Cancer Cell Lines
title_full_unstemmed Co-Encapsulation of Simvastatin and Doxorubicin into pH-Sensitive Liposomes Enhances Antitumoral Activity in Breast Cancer Cell Lines
title_short Co-Encapsulation of Simvastatin and Doxorubicin into pH-Sensitive Liposomes Enhances Antitumoral Activity in Breast Cancer Cell Lines
title_sort co-encapsulation of simvastatin and doxorubicin into ph-sensitive liposomes enhances antitumoral activity in breast cancer cell lines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9960841/
https://www.ncbi.nlm.nih.gov/pubmed/36839690
http://dx.doi.org/10.3390/pharmaceutics15020369
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