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PLGA Nanoparticles Grafted with Hyaluronic Acid to Improve Site-Specificity and Drug Dose Delivery in Osteoarthritis Nanotherapy

Nanoparticles (NPs) have a tremendous potential in medicinal applications, and recent studies have pushed the boundaries in nanotherapy, including in osteoarthritis treatments. The aim of this study was to develop new poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) surfaces decorated with hyal...

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Autores principales: Zerrillo, Luana, Gigliobianco, Maria Rosa, D’Atri, Domenico, Garcia, Joao Pedro, Baldazzi, Fabio, Ridwan, Yanto, Fuentes, Gastón, Chan, Alan, Creemers, Laura B., Censi, Roberta, Di Martino, Piera, Cruz, Luis J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268068/
https://www.ncbi.nlm.nih.gov/pubmed/35808084
http://dx.doi.org/10.3390/nano12132248
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author Zerrillo, Luana
Gigliobianco, Maria Rosa
D’Atri, Domenico
Garcia, Joao Pedro
Baldazzi, Fabio
Ridwan, Yanto
Fuentes, Gastón
Chan, Alan
Creemers, Laura B.
Censi, Roberta
Di Martino, Piera
Cruz, Luis J.
author_facet Zerrillo, Luana
Gigliobianco, Maria Rosa
D’Atri, Domenico
Garcia, Joao Pedro
Baldazzi, Fabio
Ridwan, Yanto
Fuentes, Gastón
Chan, Alan
Creemers, Laura B.
Censi, Roberta
Di Martino, Piera
Cruz, Luis J.
author_sort Zerrillo, Luana
collection PubMed
description Nanoparticles (NPs) have a tremendous potential in medicinal applications, and recent studies have pushed the boundaries in nanotherapy, including in osteoarthritis treatments. The aim of this study was to develop new poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) surfaces decorated with hyaluronic acid (HA) to enhance targeted drug specificity to the osteoarthritic knee joint. HA was selected since it binds to specific receptors expressed in many cells, such as the cluster determinant 44 (CD44), a major receptor of chondrocytes, and because of its function in the synovial fluid (SF), such as maintenance of high fluid viscosity. The PLGA polymer was grafted to sodium hyaluronate using dimethoxy-PEG (PLGA-HA) and compared with control PLGA NPs (not grafted). NPs were characterized by 1H-NMR and IR spectroscopy. Then, near-infrared (NIR) dye and gold (20 nm) were encapsulated in the formulated NPs and used to access NPs’ performance in in vitro, in vivo, and ex vivo experiments. To test the NPs’ CD44 receptor specificity, an antibody assay was performed. All NPs presented a size in the range viable for cell-uptake, no cytotoxicity to chondrocytes was registered. Although all the NPs had a high capacity to be absorbed by the cells, PLGA-HA NPs showed significantly higher affinity towards the chondrocytic C28/I2 cell line. In conclusion, PLGA NPs grafted to sodium hyaluronate showed increased binding to cartilage cells and tissue and enhanced accumulation at the target site. Thus, this study presents a safe drug-delivery system with improved receptor specificity, which may represent an advantageous alternative to current nanotherapies.
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spelling pubmed-92680682022-07-09 PLGA Nanoparticles Grafted with Hyaluronic Acid to Improve Site-Specificity and Drug Dose Delivery in Osteoarthritis Nanotherapy Zerrillo, Luana Gigliobianco, Maria Rosa D’Atri, Domenico Garcia, Joao Pedro Baldazzi, Fabio Ridwan, Yanto Fuentes, Gastón Chan, Alan Creemers, Laura B. Censi, Roberta Di Martino, Piera Cruz, Luis J. Nanomaterials (Basel) Article Nanoparticles (NPs) have a tremendous potential in medicinal applications, and recent studies have pushed the boundaries in nanotherapy, including in osteoarthritis treatments. The aim of this study was to develop new poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) surfaces decorated with hyaluronic acid (HA) to enhance targeted drug specificity to the osteoarthritic knee joint. HA was selected since it binds to specific receptors expressed in many cells, such as the cluster determinant 44 (CD44), a major receptor of chondrocytes, and because of its function in the synovial fluid (SF), such as maintenance of high fluid viscosity. The PLGA polymer was grafted to sodium hyaluronate using dimethoxy-PEG (PLGA-HA) and compared with control PLGA NPs (not grafted). NPs were characterized by 1H-NMR and IR spectroscopy. Then, near-infrared (NIR) dye and gold (20 nm) were encapsulated in the formulated NPs and used to access NPs’ performance in in vitro, in vivo, and ex vivo experiments. To test the NPs’ CD44 receptor specificity, an antibody assay was performed. All NPs presented a size in the range viable for cell-uptake, no cytotoxicity to chondrocytes was registered. Although all the NPs had a high capacity to be absorbed by the cells, PLGA-HA NPs showed significantly higher affinity towards the chondrocytic C28/I2 cell line. In conclusion, PLGA NPs grafted to sodium hyaluronate showed increased binding to cartilage cells and tissue and enhanced accumulation at the target site. Thus, this study presents a safe drug-delivery system with improved receptor specificity, which may represent an advantageous alternative to current nanotherapies. MDPI 2022-06-30 /pmc/articles/PMC9268068/ /pubmed/35808084 http://dx.doi.org/10.3390/nano12132248 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zerrillo, Luana
Gigliobianco, Maria Rosa
D’Atri, Domenico
Garcia, Joao Pedro
Baldazzi, Fabio
Ridwan, Yanto
Fuentes, Gastón
Chan, Alan
Creemers, Laura B.
Censi, Roberta
Di Martino, Piera
Cruz, Luis J.
PLGA Nanoparticles Grafted with Hyaluronic Acid to Improve Site-Specificity and Drug Dose Delivery in Osteoarthritis Nanotherapy
title PLGA Nanoparticles Grafted with Hyaluronic Acid to Improve Site-Specificity and Drug Dose Delivery in Osteoarthritis Nanotherapy
title_full PLGA Nanoparticles Grafted with Hyaluronic Acid to Improve Site-Specificity and Drug Dose Delivery in Osteoarthritis Nanotherapy
title_fullStr PLGA Nanoparticles Grafted with Hyaluronic Acid to Improve Site-Specificity and Drug Dose Delivery in Osteoarthritis Nanotherapy
title_full_unstemmed PLGA Nanoparticles Grafted with Hyaluronic Acid to Improve Site-Specificity and Drug Dose Delivery in Osteoarthritis Nanotherapy
title_short PLGA Nanoparticles Grafted with Hyaluronic Acid to Improve Site-Specificity and Drug Dose Delivery in Osteoarthritis Nanotherapy
title_sort plga nanoparticles grafted with hyaluronic acid to improve site-specificity and drug dose delivery in osteoarthritis nanotherapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9268068/
https://www.ncbi.nlm.nih.gov/pubmed/35808084
http://dx.doi.org/10.3390/nano12132248
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