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Improvement of pyrazolo[3,4-d]pyrimidines pharmacokinetic properties: nanosystem approaches for drug delivery

Pyrazolo[3,4-d]pyrimidines are a class of compounds with a good activity against several cancer cell lines. Despite the promising anticancer activity, these molecules showed a poor aqueous solubility. This issue could threat the future development of pyrazolo[3,4-d]pyrimidines as clinical drug candi...

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Autores principales: Vignaroli, Giulia, Calandro, Pierpaolo, Zamperini, Claudio, Coniglio, Federica, Iovenitti, Giulia, Tavanti, Matteo, Colecchia, David, Dreassi, Elena, Valoti, Massimo, Schenone, Silvia, Chiariello, Mario, Botta, Maurizio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761914/
https://www.ncbi.nlm.nih.gov/pubmed/26898318
http://dx.doi.org/10.1038/srep21509
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author Vignaroli, Giulia
Calandro, Pierpaolo
Zamperini, Claudio
Coniglio, Federica
Iovenitti, Giulia
Tavanti, Matteo
Colecchia, David
Dreassi, Elena
Valoti, Massimo
Schenone, Silvia
Chiariello, Mario
Botta, Maurizio
author_facet Vignaroli, Giulia
Calandro, Pierpaolo
Zamperini, Claudio
Coniglio, Federica
Iovenitti, Giulia
Tavanti, Matteo
Colecchia, David
Dreassi, Elena
Valoti, Massimo
Schenone, Silvia
Chiariello, Mario
Botta, Maurizio
author_sort Vignaroli, Giulia
collection PubMed
description Pyrazolo[3,4-d]pyrimidines are a class of compounds with a good activity against several cancer cell lines. Despite the promising anticancer activity, these molecules showed a poor aqueous solubility. This issue could threat the future development of pyrazolo[3,4-d]pyrimidines as clinical drug candidates. With the aim of improving their solubility profile and consequently their pharmacokinetic properties, we have chosen four compounds (1–4) on the base of their anti-neuroblastoma activity and we have developed albumin nanoparticles and liposomes for the selected candidates. Albumin nanoparticles and liposomes were prepared and characterized regarding size and ζ-potential distribution, polidispersity index, entrapment efficiency and activity against SH-SY5Y human neuroblastoma cell line. The most promising nanosystem, namely LP-2, was chosen to perform further studies: confocal microscopy, stability and drug release in physiological conditions, and biodistribution. Altogether, the obtained data strongly indicate that the encapsulation of pyrazolo[3,4-d]pyrimidines in liposomes represent an effective method to overcome the poor water solubility.
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spelling pubmed-47619142016-02-29 Improvement of pyrazolo[3,4-d]pyrimidines pharmacokinetic properties: nanosystem approaches for drug delivery Vignaroli, Giulia Calandro, Pierpaolo Zamperini, Claudio Coniglio, Federica Iovenitti, Giulia Tavanti, Matteo Colecchia, David Dreassi, Elena Valoti, Massimo Schenone, Silvia Chiariello, Mario Botta, Maurizio Sci Rep Article Pyrazolo[3,4-d]pyrimidines are a class of compounds with a good activity against several cancer cell lines. Despite the promising anticancer activity, these molecules showed a poor aqueous solubility. This issue could threat the future development of pyrazolo[3,4-d]pyrimidines as clinical drug candidates. With the aim of improving their solubility profile and consequently their pharmacokinetic properties, we have chosen four compounds (1–4) on the base of their anti-neuroblastoma activity and we have developed albumin nanoparticles and liposomes for the selected candidates. Albumin nanoparticles and liposomes were prepared and characterized regarding size and ζ-potential distribution, polidispersity index, entrapment efficiency and activity against SH-SY5Y human neuroblastoma cell line. The most promising nanosystem, namely LP-2, was chosen to perform further studies: confocal microscopy, stability and drug release in physiological conditions, and biodistribution. Altogether, the obtained data strongly indicate that the encapsulation of pyrazolo[3,4-d]pyrimidines in liposomes represent an effective method to overcome the poor water solubility. Nature Publishing Group 2016-02-22 /pmc/articles/PMC4761914/ /pubmed/26898318 http://dx.doi.org/10.1038/srep21509 Text en Copyright © 2016, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Vignaroli, Giulia
Calandro, Pierpaolo
Zamperini, Claudio
Coniglio, Federica
Iovenitti, Giulia
Tavanti, Matteo
Colecchia, David
Dreassi, Elena
Valoti, Massimo
Schenone, Silvia
Chiariello, Mario
Botta, Maurizio
Improvement of pyrazolo[3,4-d]pyrimidines pharmacokinetic properties: nanosystem approaches for drug delivery
title Improvement of pyrazolo[3,4-d]pyrimidines pharmacokinetic properties: nanosystem approaches for drug delivery
title_full Improvement of pyrazolo[3,4-d]pyrimidines pharmacokinetic properties: nanosystem approaches for drug delivery
title_fullStr Improvement of pyrazolo[3,4-d]pyrimidines pharmacokinetic properties: nanosystem approaches for drug delivery
title_full_unstemmed Improvement of pyrazolo[3,4-d]pyrimidines pharmacokinetic properties: nanosystem approaches for drug delivery
title_short Improvement of pyrazolo[3,4-d]pyrimidines pharmacokinetic properties: nanosystem approaches for drug delivery
title_sort improvement of pyrazolo[3,4-d]pyrimidines pharmacokinetic properties: nanosystem approaches for drug delivery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4761914/
https://www.ncbi.nlm.nih.gov/pubmed/26898318
http://dx.doi.org/10.1038/srep21509
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