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Caffeic Acid-Grafted PLGA as a Novel Material for the Design of Fluvastatin-Eluting Nanoparticles for the Prevention of Neointimal Hyperplasia

[Image: see text] Drug-eluting nanoparticles (NPs) administered by an eluting balloon represent a novel tool to prevent restenosis after angioplasty, even if the selection of the suitable drug and biodegradable material is still a matter of debate. Herein, we provide the proof of concept of the use...

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Autores principales: Bellosta, Stefano, Selmin, Francesca, Magri, Giulia, Castiglioni, Silvia, Procacci, Patrizia, Sartori, Patrizia, Scarpa, Edoardo, Tolva, Valerio, Rossi, Clara, Puoci, Francesco, Rizzello, Loris, Cilurzo, Francesco
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2022
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9937560/
https://www.ncbi.nlm.nih.gov/pubmed/36250999
http://dx.doi.org/10.1021/acs.molpharmaceut.2c00693
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author Bellosta, Stefano
Selmin, Francesca
Magri, Giulia
Castiglioni, Silvia
Procacci, Patrizia
Sartori, Patrizia
Scarpa, Edoardo
Tolva, Valerio
Rossi, Clara
Puoci, Francesco
Rizzello, Loris
Cilurzo, Francesco
author_facet Bellosta, Stefano
Selmin, Francesca
Magri, Giulia
Castiglioni, Silvia
Procacci, Patrizia
Sartori, Patrizia
Scarpa, Edoardo
Tolva, Valerio
Rossi, Clara
Puoci, Francesco
Rizzello, Loris
Cilurzo, Francesco
author_sort Bellosta, Stefano
collection PubMed
description [Image: see text] Drug-eluting nanoparticles (NPs) administered by an eluting balloon represent a novel tool to prevent restenosis after angioplasty, even if the selection of the suitable drug and biodegradable material is still a matter of debate. Herein, we provide the proof of concept of the use of a novel material obtained by combining the grafting of caffeic acid or resveratrol on a poly(lactide-co-glycolide) backbone (g-CA-PLGA or g-RV-PLGA) and the pleiotropic effects of fluvastatin chosen because of its low lipophilic profile which is challenging for the encapsulation in NPs and delivery to the artery wall cells. NPs made of such materials are biocompatible with macrophages, human smooth muscle cells (SMCs), and endothelial cells (ECs). Their cellular uptake is demonstrated and quantified by confocal microscopy using fluorescent NPs, while their distribution in the cytoplasm is verified by TEM images using NPs stained with an Ag–PVP probe appositely synthetized. g-CA-PLGA assures the best control of the FLV release from NP sizing around 180 nm and the faster SMC uptake, as demonstrated by confocal analyses. Interestingly and surprisingly, g-CA-PLGA improves the FLV efficacy to inhibit the SMC migration, without altering its effects on EC proliferation and migration. The improved trophism of NPs toward SMCs, combined with the excellent biocompatibility and low modification of the microenvironment pH upon polymer degradation, makes g-CA-PLGA a suitable material for the design of drug-eluting balloons.
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spelling pubmed-99375602023-02-18 Caffeic Acid-Grafted PLGA as a Novel Material for the Design of Fluvastatin-Eluting Nanoparticles for the Prevention of Neointimal Hyperplasia Bellosta, Stefano Selmin, Francesca Magri, Giulia Castiglioni, Silvia Procacci, Patrizia Sartori, Patrizia Scarpa, Edoardo Tolva, Valerio Rossi, Clara Puoci, Francesco Rizzello, Loris Cilurzo, Francesco Mol Pharm [Image: see text] Drug-eluting nanoparticles (NPs) administered by an eluting balloon represent a novel tool to prevent restenosis after angioplasty, even if the selection of the suitable drug and biodegradable material is still a matter of debate. Herein, we provide the proof of concept of the use of a novel material obtained by combining the grafting of caffeic acid or resveratrol on a poly(lactide-co-glycolide) backbone (g-CA-PLGA or g-RV-PLGA) and the pleiotropic effects of fluvastatin chosen because of its low lipophilic profile which is challenging for the encapsulation in NPs and delivery to the artery wall cells. NPs made of such materials are biocompatible with macrophages, human smooth muscle cells (SMCs), and endothelial cells (ECs). Their cellular uptake is demonstrated and quantified by confocal microscopy using fluorescent NPs, while their distribution in the cytoplasm is verified by TEM images using NPs stained with an Ag–PVP probe appositely synthetized. g-CA-PLGA assures the best control of the FLV release from NP sizing around 180 nm and the faster SMC uptake, as demonstrated by confocal analyses. Interestingly and surprisingly, g-CA-PLGA improves the FLV efficacy to inhibit the SMC migration, without altering its effects on EC proliferation and migration. The improved trophism of NPs toward SMCs, combined with the excellent biocompatibility and low modification of the microenvironment pH upon polymer degradation, makes g-CA-PLGA a suitable material for the design of drug-eluting balloons. American Chemical Society 2022-10-17 /pmc/articles/PMC9937560/ /pubmed/36250999 http://dx.doi.org/10.1021/acs.molpharmaceut.2c00693 Text en © 2022 American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Bellosta, Stefano
Selmin, Francesca
Magri, Giulia
Castiglioni, Silvia
Procacci, Patrizia
Sartori, Patrizia
Scarpa, Edoardo
Tolva, Valerio
Rossi, Clara
Puoci, Francesco
Rizzello, Loris
Cilurzo, Francesco
Caffeic Acid-Grafted PLGA as a Novel Material for the Design of Fluvastatin-Eluting Nanoparticles for the Prevention of Neointimal Hyperplasia
title Caffeic Acid-Grafted PLGA as a Novel Material for the Design of Fluvastatin-Eluting Nanoparticles for the Prevention of Neointimal Hyperplasia
title_full Caffeic Acid-Grafted PLGA as a Novel Material for the Design of Fluvastatin-Eluting Nanoparticles for the Prevention of Neointimal Hyperplasia
title_fullStr Caffeic Acid-Grafted PLGA as a Novel Material for the Design of Fluvastatin-Eluting Nanoparticles for the Prevention of Neointimal Hyperplasia
title_full_unstemmed Caffeic Acid-Grafted PLGA as a Novel Material for the Design of Fluvastatin-Eluting Nanoparticles for the Prevention of Neointimal Hyperplasia
title_short Caffeic Acid-Grafted PLGA as a Novel Material for the Design of Fluvastatin-Eluting Nanoparticles for the Prevention of Neointimal Hyperplasia
title_sort caffeic acid-grafted plga as a novel material for the design of fluvastatin-eluting nanoparticles for the prevention of neointimal hyperplasia
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9937560/
https://www.ncbi.nlm.nih.gov/pubmed/36250999
http://dx.doi.org/10.1021/acs.molpharmaceut.2c00693
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