In Vitro and Preclinical Antitumor Evaluation of Doxorubicin Liposomes Coated with a Cholesterol-Based Trimeric β-D-Glucopyranosyltriazole

The coating of liposomes with polyethyleneglycol (PEG) has been extensively discussed over the years as a strategy for enhancing the in vivo and in vitro stability of nanostructures, including doxorubicin-loaded liposomes. However, studies have shown some important disadvantages of the PEG molecule...

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Main Authors: Aline Teixeira Maciel e Silva, Ana Luiza Chaves Maia, Juliana de Oliveira Silva, Sued Eustáquio Mendes Miranda, Talia Silva Cantini, Andre Luis Branco de Barros, Daniel Crístian Ferreira Soares, Mariana Torquato Quezado de Magalhães, Ricardo José Alves, Gilson Andrade Ramaldes
Format: Article
Language:English
Published: MDPI AG 2023-12-01
Series:Pharmaceutics
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Online Access:https://www.mdpi.com/1999-4923/15/12/2751
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author Aline Teixeira Maciel e Silva
Ana Luiza Chaves Maia
Juliana de Oliveira Silva
Sued Eustáquio Mendes Miranda
Talia Silva Cantini
Andre Luis Branco de Barros
Daniel Crístian Ferreira Soares
Mariana Torquato Quezado de Magalhães
Ricardo José Alves
Gilson Andrade Ramaldes
author_facet Aline Teixeira Maciel e Silva
Ana Luiza Chaves Maia
Juliana de Oliveira Silva
Sued Eustáquio Mendes Miranda
Talia Silva Cantini
Andre Luis Branco de Barros
Daniel Crístian Ferreira Soares
Mariana Torquato Quezado de Magalhães
Ricardo José Alves
Gilson Andrade Ramaldes
author_sort Aline Teixeira Maciel e Silva
collection DOAJ
description The coating of liposomes with polyethyleneglycol (PEG) has been extensively discussed over the years as a strategy for enhancing the in vivo and in vitro stability of nanostructures, including doxorubicin-loaded liposomes. However, studies have shown some important disadvantages of the PEG molecule as a long-circulation agent, including the immunogenic role of PEG, which limits its clinical use in repeated doses. In this context, hydrophilic molecules as carbohydrates have been proposed as an alternative to coating liposomes. Thus, this work studied the cytotoxicity and preclinical antitumor activity of liposomes coated with a glycosyl triazole glucose (GlcL-DOX) derivative as a potential strategy against breast cancer. The glucose-coating of liposomes enhanced the storage stability compared to PEG-coated liposomes, with the suitable retention of DOX encapsulation. The antitumor activity, using a 4T1 breast cancer mouse model, shows that GlcL-DOX controlled the tumor growth in 58.5% versus 35.3% for PEG-coated liposomes (PegL-DOX). Additionally, in the preliminary analysis of the GlcL-DOX systemic toxicity, the glucose-coating liposomes reduced the body weight loss and hepatotoxicity compared to other DOX-treated groups. Therefore, GlcL-DOX could be a promising alternative for treating breast tumors. Further studies are required to elucidate the complete GlcL-DOX safety profile.
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spelling doaj.art-daf5f720cba44e9491e204f5e8702dae2023-12-22T14:32:13ZengMDPI AGPharmaceutics1999-49232023-12-011512275110.3390/pharmaceutics15122751In Vitro and Preclinical Antitumor Evaluation of Doxorubicin Liposomes Coated with a Cholesterol-Based Trimeric β-D-GlucopyranosyltriazoleAline Teixeira Maciel e Silva0Ana Luiza Chaves Maia1Juliana de Oliveira Silva2Sued Eustáquio Mendes Miranda3Talia Silva Cantini4Andre Luis Branco de Barros5Daniel Crístian Ferreira Soares6Mariana Torquato Quezado de Magalhães7Ricardo José Alves8Gilson Andrade Ramaldes9Departamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos, 6627, Belo Horizonte 31270-901, MG, BrazilDepartamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos, 6627, Belo Horizonte 31270-901, MG, BrazilDepartamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos, 6627, Belo Horizonte 31270-901, MG, BrazilDepartamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos, 6627, Belo Horizonte 31270-901, MG, BrazilDepartamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos, 6627, Belo Horizonte 31270-901, MG, BrazilDepartamento de Análises Clínicas e Toxicológicas, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos, 6627, Belo Horizonte 31270-901, MG, BrazilLaboratório de Bioengenharia, Universidade Federal de Itajubá, Rua Irmã Ivone Drumond, 200, Distrito Industrial II, Itabira 35903-087, MG, BrazilDepartamento de Bioquímica e Imunologia, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos, 6627, Belo Horizonte 31270-901, MG, BrazilDepartamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos, 6627, Belo Horizonte 31270-901, MG, BrazilDepartamento de Produtos Farmacêuticos, Faculdade de Farmácia, Universidade Federal de Minas Gerais, Av. Presidente Antônio Carlos, 6627, Belo Horizonte 31270-901, MG, BrazilThe coating of liposomes with polyethyleneglycol (PEG) has been extensively discussed over the years as a strategy for enhancing the in vivo and in vitro stability of nanostructures, including doxorubicin-loaded liposomes. However, studies have shown some important disadvantages of the PEG molecule as a long-circulation agent, including the immunogenic role of PEG, which limits its clinical use in repeated doses. In this context, hydrophilic molecules as carbohydrates have been proposed as an alternative to coating liposomes. Thus, this work studied the cytotoxicity and preclinical antitumor activity of liposomes coated with a glycosyl triazole glucose (GlcL-DOX) derivative as a potential strategy against breast cancer. The glucose-coating of liposomes enhanced the storage stability compared to PEG-coated liposomes, with the suitable retention of DOX encapsulation. The antitumor activity, using a 4T1 breast cancer mouse model, shows that GlcL-DOX controlled the tumor growth in 58.5% versus 35.3% for PEG-coated liposomes (PegL-DOX). Additionally, in the preliminary analysis of the GlcL-DOX systemic toxicity, the glucose-coating liposomes reduced the body weight loss and hepatotoxicity compared to other DOX-treated groups. Therefore, GlcL-DOX could be a promising alternative for treating breast tumors. Further studies are required to elucidate the complete GlcL-DOX safety profile.https://www.mdpi.com/1999-4923/15/12/2751liposomessurface coatingcarbohydratesantitumor activity
spellingShingle Aline Teixeira Maciel e Silva
Ana Luiza Chaves Maia
Juliana de Oliveira Silva
Sued Eustáquio Mendes Miranda
Talia Silva Cantini
Andre Luis Branco de Barros
Daniel Crístian Ferreira Soares
Mariana Torquato Quezado de Magalhães
Ricardo José Alves
Gilson Andrade Ramaldes
In Vitro and Preclinical Antitumor Evaluation of Doxorubicin Liposomes Coated with a Cholesterol-Based Trimeric β-D-Glucopyranosyltriazole
Pharmaceutics
liposomes
surface coating
carbohydrates
antitumor activity
title In Vitro and Preclinical Antitumor Evaluation of Doxorubicin Liposomes Coated with a Cholesterol-Based Trimeric β-D-Glucopyranosyltriazole
title_full In Vitro and Preclinical Antitumor Evaluation of Doxorubicin Liposomes Coated with a Cholesterol-Based Trimeric β-D-Glucopyranosyltriazole
title_fullStr In Vitro and Preclinical Antitumor Evaluation of Doxorubicin Liposomes Coated with a Cholesterol-Based Trimeric β-D-Glucopyranosyltriazole
title_full_unstemmed In Vitro and Preclinical Antitumor Evaluation of Doxorubicin Liposomes Coated with a Cholesterol-Based Trimeric β-D-Glucopyranosyltriazole
title_short In Vitro and Preclinical Antitumor Evaluation of Doxorubicin Liposomes Coated with a Cholesterol-Based Trimeric β-D-Glucopyranosyltriazole
title_sort in vitro and preclinical antitumor evaluation of doxorubicin liposomes coated with a cholesterol based trimeric β d glucopyranosyltriazole
topic liposomes
surface coating
carbohydrates
antitumor activity
url https://www.mdpi.com/1999-4923/15/12/2751
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