Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading

Victoria Leonhard,1,2 Roxana V Alasino,1,2 Ismael D Bianco,1–3 Ariel G Garro,1 Valeria Heredia,1 Dante M Beltramo1,2,4 1Centro de Excelencia en Productos y Procesos de Córdoba (CEPROCOR), Córdoba, Argentina; 2Consejo Nacional de Investigaciones Científicas...

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Autores principales:	Leonhard V, Alasino RV, Bianco ID, Garro AG, Heredia V, Beltramo DM
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2015
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/6e774fff02904b6da8cdc9bc0bd9a0b6
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spelling	oai:doaj.org-article:6e774fff02904b6da8cdc9bc0bd9a0b62021-12-02T03:11:48ZBiochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading1178-2013https://doaj.org/article/6e774fff02904b6da8cdc9bc0bd9a0b62015-05-01T00:00:00Zhttp://www.dovepress.com/biochemical-characterization-of-the-interactions-between-doxorubicin-a-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Victoria Leonhard,1,2 Roxana V Alasino,1,2 Ismael D Bianco,1–3 Ariel G Garro,1 Valeria Heredia,1 Dante M Beltramo1,2,4 1Centro de Excelencia en Productos y Procesos de Córdoba (CEPROCOR), Córdoba, Argentina; 2Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina; 3Departamento de Ciencias Exactas, Físicas y Naturales, Universidad Nacional de La Rioja, La Rioja, Argentina; 4Laboratorio de Biotecnología, Facultad de Ciencias Químicas, Universidad Católica de Córdoba, Córdoba, Argentina Abstract: Doxorubicin (Dox) is an anthracycline anticancer drug with high water solubility, whose use is limited primarily due to significant side effects. In this study it is shown that Dox interacts with monosialoglycosphingolipid (GM1) ganglioside micelles primarily through hydrophobic interactions independent of pH and ionic strength. In addition, Dox can be incorporated even into GM1 micelles already containing highly hydrophobic paclitaxel (Ptx). However, it was not possible to incorporate Ptx into Dox-containing GM1 micelles, suggesting that Dox could be occupying a more external position in the micelles. This result is in agreement with a higher hydrolysis of Dox than of Ptx when micelles were incubated at alkaline pH. The loading of Dox into GM1 micelles was observed over a broad range of temperature (4°C–55°C). Furthermore, Dox-loaded micelles were stable in aqueous solutions exhibiting no aggregation or precipitation for up to 2 months when kept at 4°C–25°C and even after freeze–thawing cycles. Upon exposure to blood components, Dox-containing micelles were observed to interact with human serum albumin. However, the amount of human serum albumin that ended up being associated to the micelles was inversely related to the amount of Dox, suggesting that both could share their binding sites. In vitro studies on Hep2 cells showed that the cellular uptake and cytotoxic activity of Dox and Ptx from the micellar complexes were similar to those of the free form of these drugs, even when the micelle was covered with albumin. These results support the idea of the existence of different nano-domains in a single micelle and the fact that this micellar model could be used as a platform for loading and delivering hydrophobic and hydrophilic active pharmaceutical ingredients. Keywords: cancer drugs, nano-domains, drug delivery, hydrophobic interactionsLeonhard VAlasino RVBianco IDGarro AGHeredia VBeltramo DMDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2015, Iss default, Pp 3377-3388 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Leonhard V Alasino RV Bianco ID Garro AG Heredia V Beltramo DM Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading
description	Victoria Leonhard,1,2 Roxana V Alasino,1,2 Ismael D Bianco,1–3 Ariel G Garro,1 Valeria Heredia,1 Dante M Beltramo1,2,4 1Centro de Excelencia en Productos y Procesos de Córdoba (CEPROCOR), Córdoba, Argentina; 2Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina; 3Departamento de Ciencias Exactas, Físicas y Naturales, Universidad Nacional de La Rioja, La Rioja, Argentina; 4Laboratorio de Biotecnología, Facultad de Ciencias Químicas, Universidad Católica de Córdoba, Córdoba, Argentina Abstract: Doxorubicin (Dox) is an anthracycline anticancer drug with high water solubility, whose use is limited primarily due to significant side effects. In this study it is shown that Dox interacts with monosialoglycosphingolipid (GM1) ganglioside micelles primarily through hydrophobic interactions independent of pH and ionic strength. In addition, Dox can be incorporated even into GM1 micelles already containing highly hydrophobic paclitaxel (Ptx). However, it was not possible to incorporate Ptx into Dox-containing GM1 micelles, suggesting that Dox could be occupying a more external position in the micelles. This result is in agreement with a higher hydrolysis of Dox than of Ptx when micelles were incubated at alkaline pH. The loading of Dox into GM1 micelles was observed over a broad range of temperature (4°C–55°C). Furthermore, Dox-loaded micelles were stable in aqueous solutions exhibiting no aggregation or precipitation for up to 2 months when kept at 4°C–25°C and even after freeze–thawing cycles. Upon exposure to blood components, Dox-containing micelles were observed to interact with human serum albumin. However, the amount of human serum albumin that ended up being associated to the micelles was inversely related to the amount of Dox, suggesting that both could share their binding sites. In vitro studies on Hep2 cells showed that the cellular uptake and cytotoxic activity of Dox and Ptx from the micellar complexes were similar to those of the free form of these drugs, even when the micelle was covered with albumin. These results support the idea of the existence of different nano-domains in a single micelle and the fact that this micellar model could be used as a platform for loading and delivering hydrophobic and hydrophilic active pharmaceutical ingredients. Keywords: cancer drugs, nano-domains, drug delivery, hydrophobic interactions
format	article
author	Leonhard V Alasino RV Bianco ID Garro AG Heredia V Beltramo DM
author_facet	Leonhard V Alasino RV Bianco ID Garro AG Heredia V Beltramo DM
author_sort	Leonhard V
title	Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading
title_short	Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading
title_full	Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading
title_fullStr	Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading
title_full_unstemmed	Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading
title_sort	biochemical characterization of the interactions between doxorubicin and lipidic gm1 micelles with or without paclitaxel loading
publisher	Dove Medical Press
publishDate	2015
url	https://doaj.org/article/6e774fff02904b6da8cdc9bc0bd9a0b6
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Biochemical characterization of the interactions between doxorubicin and lipidic GM1 micelles with or without paclitaxel loading

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