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

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Dpto. Inorgánica, Orgánica y Bioquímica. School of Pharmacy, University of Castilla-La Mancha, 02071 Albacete, Spain
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Oncología traslacional, Centro Regional de Investigaciones Biomédicas, University of Castilla-La Mancha, 02071 Albacete, Spain
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Dpto. Química Física. School of Pharmacy, University of Castilla-La Mancha, 02071 Albacete, Spain
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Dpto. Inorgánica, Orgánica y Bioquímica. Facultad de Ciencias y Tecnologías Químicas, University of Castilla-La Mancha, 13075 Ciudad Real, Spain
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Unidad Asociada Neurodeath CSIC-UCLM, Dpto. de Ciencias Médicas, School of Pharmacy, University of Castilla-La Mancha, 02071 Albacete, Spain
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Instituto de Energías Renovables, University of Castilla-La Mancha, 02071 Albacete, Spain
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Netherlands Organisation for Scientific Research (NWO), [email protected], 38000 Grenoble, France
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NCD beamline, ALBA Synchrotron Light Source, Carrer de la Llum 2-26, 08290 Cerdanyola del Vallès, Spain
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Hospital Clínico San Carlos, 28036 Madrid, Spain
*
Authors to whom correspondence should be addressed.
Nanomaterials 2019, 9(9), 1208; https://doi.org/10.3390/nano9091208
Received: 31 July 2019 / Revised: 23 August 2019 / Accepted: 26 August 2019 / Published: 27 August 2019
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. View Full-Text
Keywords: dasatinib; breast cancer; poly(cyclohexene phthalate); polymeric nanoparticles dasatinib; breast cancer; poly(cyclohexene phthalate); polymeric nanoparticles
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Niza, E.; Nieto-Jiménez, C.; Noblejas-López, M.M.; Bravo, I.; Castro-Osma, J.A.; de la Cruz-Martínez, F.; Martínez de Sarasa Buchaca, M.; Posadas, I.; Canales-Vázquez, J.; Lara-Sanchez, A.; Hermida-Merino, D.; Solano, E.; Ocaña, A.; Alonso-Moreno, C. Poly(Cyclohexene Phthalate) Nanoparticles for Controlled Dasatinib Delivery in Breast Cancer Therapy. Nanomaterials 2019, 9, 1208.

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