Preclinical toxicological study of long-circulating and fusogenic liposomes co-encapsulating paclitaxel and doxorubicin in synergic ratio

Combination therapy between paclitaxel (PTX) and doxorubicin (DXR) is applied as the first-line treatment of breast cancer. Co-administration of drugs at synergistic ratio for treatment is facilitated with the use of nanocarriers, such as liposomes. However, despite the high response rate of solid t...

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Autores principales:	Marjorie Coimbra Roque, Caroline Dohanik da Silva, Marthin Raboch Lempek, Geovanni Dantas Cassali, André Luís Branco de Barros, Marília Martins Melo, Mônica Cristina Oliveira
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Liposomes Doxorubicin Paclitaxel Co-administration Acute toxicity Breast cancer Therapeutics. Pharmacology RM1-950
Acceso en línea:	https://doaj.org/article/6877ad28e1be4f4dab58f15d3bd95e47
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spelling	oai:doaj.org-article:6877ad28e1be4f4dab58f15d3bd95e472021-11-14T04:29:27ZPreclinical toxicological study of long-circulating and fusogenic liposomes co-encapsulating paclitaxel and doxorubicin in synergic ratio0753-332210.1016/j.biopha.2021.112307https://doaj.org/article/6877ad28e1be4f4dab58f15d3bd95e472021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S075333222101091Xhttps://doaj.org/toc/0753-3322Combination therapy between paclitaxel (PTX) and doxorubicin (DXR) is applied as the first-line treatment of breast cancer. Co-administration of drugs at synergistic ratio for treatment is facilitated with the use of nanocarriers, such as liposomes. However, despite the high response rate of solid tumors to this combination, a synergism of cardiotoxicity may limit the use. Thus, the objective of this work was to investigate the toxicity of long-circulating and fusogenic liposomes co-encapsulating PTX and DXR at the synergistic molar ratio (1:10) (LCFL-PTX/DXR). For this, clinical chemistry, histopathological analysis and electrocardiographic exams were performed on female Balb/c mice that received a single intravenous dose of LCFL-PTX/DXR. The results of the study indicated that the LD50 dose range (lethal dose for 50% of animals) of the LCFL-PTX/DXR treatment (28.9–34.7 mg/kg) is much higher than that found for free PTX/DXR treatment (20.8–23.1 mg/kg). In addition, liposomes promoted cardiac protection by not raising CK-MB levels in animals, keeping cardiomyocytes without injury or electrocardiographic changes. After 14 days of treatment, free PTX/DXR caused prolongation of the QRS interval when compared to LCFL-PTX/DXR treatment at the same dose (37.0 ± 5.01 ms and 30.83 ± 2.62 ms, respectively, with p = 0.017). The survival rate of animals treated with LCFL-PTX/DXR was three times higher than that of those treated with free drugs. Thus, it was established that the toxicity of LCFL-PTX/DXR is reduced compared to the combination of free PTX/DXR and this platform has advantages for the clinical treatment of breast cancer.Marjorie Coimbra RoqueCaroline Dohanik da SilvaMarthin Raboch LempekGeovanni Dantas CassaliAndré Luís Branco de BarrosMarília Martins MeloMônica Cristina OliveiraElsevierarticleLiposomesDoxorubicinPaclitaxelCo-administrationAcute toxicityBreast cancerTherapeutics. PharmacologyRM1-950ENBiomedicine & Pharmacotherapy, Vol 144, Iss , Pp 112307- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Liposomes Doxorubicin Paclitaxel Co-administration Acute toxicity Breast cancer Therapeutics. Pharmacology RM1-950
spellingShingle	Liposomes Doxorubicin Paclitaxel Co-administration Acute toxicity Breast cancer Therapeutics. Pharmacology RM1-950 Marjorie Coimbra Roque Caroline Dohanik da Silva Marthin Raboch Lempek Geovanni Dantas Cassali André Luís Branco de Barros Marília Martins Melo Mônica Cristina Oliveira Preclinical toxicological study of long-circulating and fusogenic liposomes co-encapsulating paclitaxel and doxorubicin in synergic ratio
description	Combination therapy between paclitaxel (PTX) and doxorubicin (DXR) is applied as the first-line treatment of breast cancer. Co-administration of drugs at synergistic ratio for treatment is facilitated with the use of nanocarriers, such as liposomes. However, despite the high response rate of solid tumors to this combination, a synergism of cardiotoxicity may limit the use. Thus, the objective of this work was to investigate the toxicity of long-circulating and fusogenic liposomes co-encapsulating PTX and DXR at the synergistic molar ratio (1:10) (LCFL-PTX/DXR). For this, clinical chemistry, histopathological analysis and electrocardiographic exams were performed on female Balb/c mice that received a single intravenous dose of LCFL-PTX/DXR. The results of the study indicated that the LD50 dose range (lethal dose for 50% of animals) of the LCFL-PTX/DXR treatment (28.9–34.7 mg/kg) is much higher than that found for free PTX/DXR treatment (20.8–23.1 mg/kg). In addition, liposomes promoted cardiac protection by not raising CK-MB levels in animals, keeping cardiomyocytes without injury or electrocardiographic changes. After 14 days of treatment, free PTX/DXR caused prolongation of the QRS interval when compared to LCFL-PTX/DXR treatment at the same dose (37.0 ± 5.01 ms and 30.83 ± 2.62 ms, respectively, with p = 0.017). The survival rate of animals treated with LCFL-PTX/DXR was three times higher than that of those treated with free drugs. Thus, it was established that the toxicity of LCFL-PTX/DXR is reduced compared to the combination of free PTX/DXR and this platform has advantages for the clinical treatment of breast cancer.
format	article
author	Marjorie Coimbra Roque Caroline Dohanik da Silva Marthin Raboch Lempek Geovanni Dantas Cassali André Luís Branco de Barros Marília Martins Melo Mônica Cristina Oliveira
author_facet	Marjorie Coimbra Roque Caroline Dohanik da Silva Marthin Raboch Lempek Geovanni Dantas Cassali André Luís Branco de Barros Marília Martins Melo Mônica Cristina Oliveira
author_sort	Marjorie Coimbra Roque
title	Preclinical toxicological study of long-circulating and fusogenic liposomes co-encapsulating paclitaxel and doxorubicin in synergic ratio
title_short	Preclinical toxicological study of long-circulating and fusogenic liposomes co-encapsulating paclitaxel and doxorubicin in synergic ratio
title_full	Preclinical toxicological study of long-circulating and fusogenic liposomes co-encapsulating paclitaxel and doxorubicin in synergic ratio
title_fullStr	Preclinical toxicological study of long-circulating and fusogenic liposomes co-encapsulating paclitaxel and doxorubicin in synergic ratio
title_full_unstemmed	Preclinical toxicological study of long-circulating and fusogenic liposomes co-encapsulating paclitaxel and doxorubicin in synergic ratio
title_sort	preclinical toxicological study of long-circulating and fusogenic liposomes co-encapsulating paclitaxel and doxorubicin in synergic ratio
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/6877ad28e1be4f4dab58f15d3bd95e47
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Preclinical toxicological study of long-circulating and fusogenic liposomes co-encapsulating paclitaxel and doxorubicin in synergic ratio

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