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Poly(Cyclohexene Phthalate) Nanoparticles for Controlled Dasatinib Delivery in Breast Cancer Therapy

The effect on the activity in breast cancer models of the small tyrosine kinase inhibitor dasatinib (DAS), either alone or in combination with other antitumoral agents, has been recently explored. However, DAS is characterized by its low and highly pH-dependent solubility, which could lead to poor u...

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Autores principales: Niza, Enrique, Nieto-Jiménez, Cristina, Noblejas-López, María del Mar, Bravo, Iván, Castro-Osma, José Antonio, de la Cruz-Martínez, Felipe, Martínez de Sarasa Buchaca, Marc, Posadas, Inmaculada, Canales-Vázquez, Jesús, Lara-Sanchez, Agustín, Hermida-Merino, Daniel, Solano, Eduardo, Ocaña, Alberto, Alonso-Moreno, Carlos
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780527/
https://www.ncbi.nlm.nih.gov/pubmed/31461998
http://dx.doi.org/10.3390/nano9091208
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author Niza, Enrique
Nieto-Jiménez, Cristina
Noblejas-López, María del Mar
Bravo, Iván
Castro-Osma, José Antonio
de la Cruz-Martínez, Felipe
Martínez de Sarasa Buchaca, Marc
Posadas, Inmaculada
Canales-Vázquez, Jesús
Lara-Sanchez, Agustín
Hermida-Merino, Daniel
Solano, Eduardo
Ocaña, Alberto
Alonso-Moreno, Carlos
author_facet Niza, Enrique
Nieto-Jiménez, Cristina
Noblejas-López, María del Mar
Bravo, Iván
Castro-Osma, José Antonio
de la Cruz-Martínez, Felipe
Martínez de Sarasa Buchaca, Marc
Posadas, Inmaculada
Canales-Vázquez, Jesús
Lara-Sanchez, Agustín
Hermida-Merino, Daniel
Solano, Eduardo
Ocaña, Alberto
Alonso-Moreno, Carlos
author_sort Niza, Enrique
collection PubMed
description The effect on the activity in breast cancer models of the small tyrosine kinase inhibitor dasatinib (DAS), either alone or in combination with other antitumoral agents, has been recently explored. However, DAS is characterized by its low and highly pH-dependent solubility, which could lead to poor uptake of the drug limiting its tumoral efficacy. Thus far, the development of safe and efficient delivery vehicles of DAS to improve the therapeutic efficacy minimizing the toxicity profile is still required. In this work, a biodegradable and biocompatible polyester is assessed, for the first time, as raw material for the generation of polymeric nanoparticles (NPs). NPs of 100 nm with a narrow polydispersity were formulated for the encapsulation of DAS. The enzymatic and cellular degradation of the new drug delivery system has been studied, and the toxicity and blood compatibility evaluated for its potential clinical use. The new material used for the generation of nanoparticles led to encapsulate DAS in an efficient manner with quicker release DAS profile when compared with the FDA-approved biopolymer Polylactide. The new DAS-loaded polymeric nanocarrier gave a superior efficacy when compared to free DAS with no difference in the mechanism of action. The new NPs shown to be a promising DAS delivery system to be further evaluated for breast cancer treatment.
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spelling pubmed-67805272019-10-30 Poly(Cyclohexene Phthalate) Nanoparticles for Controlled Dasatinib Delivery in Breast Cancer Therapy Niza, Enrique Nieto-Jiménez, Cristina Noblejas-López, María del Mar Bravo, Iván Castro-Osma, José Antonio de la Cruz-Martínez, Felipe Martínez de Sarasa Buchaca, Marc Posadas, Inmaculada Canales-Vázquez, Jesús Lara-Sanchez, Agustín Hermida-Merino, Daniel Solano, Eduardo Ocaña, Alberto Alonso-Moreno, Carlos Nanomaterials (Basel) Article The effect on the activity in breast cancer models of the small tyrosine kinase inhibitor dasatinib (DAS), either alone or in combination with other antitumoral agents, has been recently explored. However, DAS is characterized by its low and highly pH-dependent solubility, which could lead to poor uptake of the drug limiting its tumoral efficacy. Thus far, the development of safe and efficient delivery vehicles of DAS to improve the therapeutic efficacy minimizing the toxicity profile is still required. In this work, a biodegradable and biocompatible polyester is assessed, for the first time, as raw material for the generation of polymeric nanoparticles (NPs). NPs of 100 nm with a narrow polydispersity were formulated for the encapsulation of DAS. The enzymatic and cellular degradation of the new drug delivery system has been studied, and the toxicity and blood compatibility evaluated for its potential clinical use. The new material used for the generation of nanoparticles led to encapsulate DAS in an efficient manner with quicker release DAS profile when compared with the FDA-approved biopolymer Polylactide. The new DAS-loaded polymeric nanocarrier gave a superior efficacy when compared to free DAS with no difference in the mechanism of action. The new NPs shown to be a promising DAS delivery system to be further evaluated for breast cancer treatment. MDPI 2019-08-27 /pmc/articles/PMC6780527/ /pubmed/31461998 http://dx.doi.org/10.3390/nano9091208 Text en © 2019 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
Niza, Enrique
Nieto-Jiménez, Cristina
Noblejas-López, María del Mar
Bravo, Iván
Castro-Osma, José Antonio
de la Cruz-Martínez, Felipe
Martínez de Sarasa Buchaca, Marc
Posadas, Inmaculada
Canales-Vázquez, Jesús
Lara-Sanchez, Agustín
Hermida-Merino, Daniel
Solano, Eduardo
Ocaña, Alberto
Alonso-Moreno, Carlos
Poly(Cyclohexene Phthalate) Nanoparticles for Controlled Dasatinib Delivery in Breast Cancer Therapy
title Poly(Cyclohexene Phthalate) Nanoparticles for Controlled Dasatinib Delivery in Breast Cancer Therapy
title_full Poly(Cyclohexene Phthalate) Nanoparticles for Controlled Dasatinib Delivery in Breast Cancer Therapy
title_fullStr Poly(Cyclohexene Phthalate) Nanoparticles for Controlled Dasatinib Delivery in Breast Cancer Therapy
title_full_unstemmed Poly(Cyclohexene Phthalate) Nanoparticles for Controlled Dasatinib Delivery in Breast Cancer Therapy
title_short Poly(Cyclohexene Phthalate) Nanoparticles for Controlled Dasatinib Delivery in Breast Cancer Therapy
title_sort poly(cyclohexene phthalate) nanoparticles for controlled dasatinib delivery in breast cancer therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780527/
https://www.ncbi.nlm.nih.gov/pubmed/31461998
http://dx.doi.org/10.3390/nano9091208
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