Cargando…
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...
Autores principales: | , , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1783457155313041408 |
---|---|
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. |
format | Online Article Text |
id | pubmed-6780527 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT nizaenrique polycyclohexenephthalatenanoparticlesforcontrolleddasatinibdeliveryinbreastcancertherapy AT nietojimenezcristina polycyclohexenephthalatenanoparticlesforcontrolleddasatinibdeliveryinbreastcancertherapy AT noblejaslopezmariadelmar polycyclohexenephthalatenanoparticlesforcontrolleddasatinibdeliveryinbreastcancertherapy AT bravoivan polycyclohexenephthalatenanoparticlesforcontrolleddasatinibdeliveryinbreastcancertherapy AT castroosmajoseantonio polycyclohexenephthalatenanoparticlesforcontrolleddasatinibdeliveryinbreastcancertherapy AT delacruzmartinezfelipe polycyclohexenephthalatenanoparticlesforcontrolleddasatinibdeliveryinbreastcancertherapy AT martinezdesarasabuchacamarc polycyclohexenephthalatenanoparticlesforcontrolleddasatinibdeliveryinbreastcancertherapy AT posadasinmaculada polycyclohexenephthalatenanoparticlesforcontrolleddasatinibdeliveryinbreastcancertherapy AT canalesvazquezjesus polycyclohexenephthalatenanoparticlesforcontrolleddasatinibdeliveryinbreastcancertherapy AT larasanchezagustin polycyclohexenephthalatenanoparticlesforcontrolleddasatinibdeliveryinbreastcancertherapy AT hermidamerinodaniel polycyclohexenephthalatenanoparticlesforcontrolleddasatinibdeliveryinbreastcancertherapy AT solanoeduardo polycyclohexenephthalatenanoparticlesforcontrolleddasatinibdeliveryinbreastcancertherapy AT ocanaalberto polycyclohexenephthalatenanoparticlesforcontrolleddasatinibdeliveryinbreastcancertherapy AT alonsomorenocarlos polycyclohexenephthalatenanoparticlesforcontrolleddasatinibdeliveryinbreastcancertherapy |