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Characterization and Mathematical Modeling of Alginate/Chitosan-Based Nanoparticles Releasing the Chemokine CXCL12 to Attract Glioblastoma Cells

Chitosan (Chit) currently used to prepare nanoparticles (NPs) for brain application can be complexed with negatively charged polymers such as alginate (Alg) to better entrap positively charged molecules such as CXCL12. A sustained CXCL12 gradient created by a delivery system can be used, as a therap...

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Autores principales: Gascon, Suzanne, Giraldo Solano, Angéla, El Kheir, Wiam, Therriault, Hélène, Berthelin, Pierre, Cattier, Bettina, Marcos, Bernard, Virgilio, Nick, Paquette, Benoit, Faucheux, Nathalie, Lauzon, Marc-Antoine
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238026/
https://www.ncbi.nlm.nih.gov/pubmed/32295255
http://dx.doi.org/10.3390/pharmaceutics12040356
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author Gascon, Suzanne
Giraldo Solano, Angéla
El Kheir, Wiam
Therriault, Hélène
Berthelin, Pierre
Cattier, Bettina
Marcos, Bernard
Virgilio, Nick
Paquette, Benoit
Faucheux, Nathalie
Lauzon, Marc-Antoine
author_facet Gascon, Suzanne
Giraldo Solano, Angéla
El Kheir, Wiam
Therriault, Hélène
Berthelin, Pierre
Cattier, Bettina
Marcos, Bernard
Virgilio, Nick
Paquette, Benoit
Faucheux, Nathalie
Lauzon, Marc-Antoine
author_sort Gascon, Suzanne
collection PubMed
description Chitosan (Chit) currently used to prepare nanoparticles (NPs) for brain application can be complexed with negatively charged polymers such as alginate (Alg) to better entrap positively charged molecules such as CXCL12. A sustained CXCL12 gradient created by a delivery system can be used, as a therapeutic approach, to control the migration of cancerous cells infiltrated in peri-tumoral tissues similar to those of glioblastoma multiforme (GBM). For this purpose, we prepared Alg/Chit NPs entrapping CXCL12 and characterized them. We demonstrated that Alg/Chit NPs, with an average size of ~250 nm, entrapped CXCL12 with ~98% efficiency for initial mass loadings varying from 0.372 to 1.490 µg/mg NPs. The release kinetic profiles of CXCL12 were dependent on the initial mass loading, and the released chemokine from NPs after seven days reached 12.6%, 32.3%, and 59.9% of cumulative release for initial contents of 0.372, 0.744, and 1.490 µg CXCL12/mg NPs, respectively. Mathematical modeling of released kinetics showed a predominant diffusive process with strong interactions between Alg and CXCL12. The CXCL12-NPs were not toxic and did not promote F98 GBM cell proliferation, while the released CXCL12 kept its chemotaxis effect. Thus, we developed an efficient and tunable CXCL12 delivery system as a promising therapeutic strategy that aims to be injected into a hydrogel used to fill the cavity after surgical tumor resection. This system will be used to attract infiltrated GBM cells prior to their elimination by conventional treatment without affecting a large zone of healthy brain tissue.
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spelling pubmed-72380262020-05-28 Characterization and Mathematical Modeling of Alginate/Chitosan-Based Nanoparticles Releasing the Chemokine CXCL12 to Attract Glioblastoma Cells Gascon, Suzanne Giraldo Solano, Angéla El Kheir, Wiam Therriault, Hélène Berthelin, Pierre Cattier, Bettina Marcos, Bernard Virgilio, Nick Paquette, Benoit Faucheux, Nathalie Lauzon, Marc-Antoine Pharmaceutics Article Chitosan (Chit) currently used to prepare nanoparticles (NPs) for brain application can be complexed with negatively charged polymers such as alginate (Alg) to better entrap positively charged molecules such as CXCL12. A sustained CXCL12 gradient created by a delivery system can be used, as a therapeutic approach, to control the migration of cancerous cells infiltrated in peri-tumoral tissues similar to those of glioblastoma multiforme (GBM). For this purpose, we prepared Alg/Chit NPs entrapping CXCL12 and characterized them. We demonstrated that Alg/Chit NPs, with an average size of ~250 nm, entrapped CXCL12 with ~98% efficiency for initial mass loadings varying from 0.372 to 1.490 µg/mg NPs. The release kinetic profiles of CXCL12 were dependent on the initial mass loading, and the released chemokine from NPs after seven days reached 12.6%, 32.3%, and 59.9% of cumulative release for initial contents of 0.372, 0.744, and 1.490 µg CXCL12/mg NPs, respectively. Mathematical modeling of released kinetics showed a predominant diffusive process with strong interactions between Alg and CXCL12. The CXCL12-NPs were not toxic and did not promote F98 GBM cell proliferation, while the released CXCL12 kept its chemotaxis effect. Thus, we developed an efficient and tunable CXCL12 delivery system as a promising therapeutic strategy that aims to be injected into a hydrogel used to fill the cavity after surgical tumor resection. This system will be used to attract infiltrated GBM cells prior to their elimination by conventional treatment without affecting a large zone of healthy brain tissue. MDPI 2020-04-14 /pmc/articles/PMC7238026/ /pubmed/32295255 http://dx.doi.org/10.3390/pharmaceutics12040356 Text en © 2020 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
Gascon, Suzanne
Giraldo Solano, Angéla
El Kheir, Wiam
Therriault, Hélène
Berthelin, Pierre
Cattier, Bettina
Marcos, Bernard
Virgilio, Nick
Paquette, Benoit
Faucheux, Nathalie
Lauzon, Marc-Antoine
Characterization and Mathematical Modeling of Alginate/Chitosan-Based Nanoparticles Releasing the Chemokine CXCL12 to Attract Glioblastoma Cells
title Characterization and Mathematical Modeling of Alginate/Chitosan-Based Nanoparticles Releasing the Chemokine CXCL12 to Attract Glioblastoma Cells
title_full Characterization and Mathematical Modeling of Alginate/Chitosan-Based Nanoparticles Releasing the Chemokine CXCL12 to Attract Glioblastoma Cells
title_fullStr Characterization and Mathematical Modeling of Alginate/Chitosan-Based Nanoparticles Releasing the Chemokine CXCL12 to Attract Glioblastoma Cells
title_full_unstemmed Characterization and Mathematical Modeling of Alginate/Chitosan-Based Nanoparticles Releasing the Chemokine CXCL12 to Attract Glioblastoma Cells
title_short Characterization and Mathematical Modeling of Alginate/Chitosan-Based Nanoparticles Releasing the Chemokine CXCL12 to Attract Glioblastoma Cells
title_sort characterization and mathematical modeling of alginate/chitosan-based nanoparticles releasing the chemokine cxcl12 to attract glioblastoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238026/
https://www.ncbi.nlm.nih.gov/pubmed/32295255
http://dx.doi.org/10.3390/pharmaceutics12040356
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