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Compartmentalized Polymeric Nanoparticles Deliver Vancomycin in a pH-Responsive Manner

Vancomycin (VCM) is a last resort antibiotic in the treatment of severe Gram-positive infections. However, its administration is limited by several drawbacks such as: strong pH-dependent charge, tendency to aggregate, low bioavailability, and poor cellular uptake. These drawbacks were circumvented b...

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Autores principales: Ural, Merve Seray, Menéndez-Miranda, Mario, Salzano, Giuseppina, Mathurin, Jérémie, Aybeke, Ece Neslihan, Deniset-Besseau, Ariane, Dazzi, Alexandre, Porcino, Marianna, Martineau-Corcos, Charlotte, Gref, Ruxandra
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8709497/
https://www.ncbi.nlm.nih.gov/pubmed/34959274
http://dx.doi.org/10.3390/pharmaceutics13121992
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author Ural, Merve Seray
Menéndez-Miranda, Mario
Salzano, Giuseppina
Mathurin, Jérémie
Aybeke, Ece Neslihan
Deniset-Besseau, Ariane
Dazzi, Alexandre
Porcino, Marianna
Martineau-Corcos, Charlotte
Gref, Ruxandra
author_facet Ural, Merve Seray
Menéndez-Miranda, Mario
Salzano, Giuseppina
Mathurin, Jérémie
Aybeke, Ece Neslihan
Deniset-Besseau, Ariane
Dazzi, Alexandre
Porcino, Marianna
Martineau-Corcos, Charlotte
Gref, Ruxandra
author_sort Ural, Merve Seray
collection PubMed
description Vancomycin (VCM) is a last resort antibiotic in the treatment of severe Gram-positive infections. However, its administration is limited by several drawbacks such as: strong pH-dependent charge, tendency to aggregate, low bioavailability, and poor cellular uptake. These drawbacks were circumvented by engineering pH-responsive nanoparticles (NPs) capable to incorporate high VCM payload and deliver it specifically at slightly acidic pH corresponding to infection sites. Taking advantage of peculiar physicochemical properties of VCM, here we show how to incorporate VCM efficiently in biodegradable NPs made of poly(lactic-co-glycolic acid) and polylactic acid (co)polymers. The NPs were prepared by a simple and reproducible method, establishing strong electrostatic interactions between VCM and the (co)polymers’ end groups. VCM payloads reached up to 25 wt%. The drug loading mechanism was investigated by solid state nuclear magnetic resonance spectroscopy. The engineered NPs were characterized by a set of advanced physicochemical methods, which allowed examining their morphology, internal structures, and chemical composition on an individual NP basis. The compartmentalized structure of NPs was evidenced by cryogenic transmission electronic microscopy, whereas the chemical composition of the NPs’ top layers and core was obtained by electron microscopies associated with energy-dispersive X-ray spectroscopy. Noteworthy, atomic force microscopy coupled to infrared spectroscopy allowed mapping the drug location and gave semiquantitative information about the loadings of individual NPs. In addition, the NPs were stable upon storage and did not release the incorporated drug at neutral pH. Interestingly, a slight acidification of the medium induced a rapid VCM release. The compartmentalized NPs could find potential applications for controlled VCM release at an infected site with local acidic pH.
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spelling pubmed-87094972021-12-25 Compartmentalized Polymeric Nanoparticles Deliver Vancomycin in a pH-Responsive Manner Ural, Merve Seray Menéndez-Miranda, Mario Salzano, Giuseppina Mathurin, Jérémie Aybeke, Ece Neslihan Deniset-Besseau, Ariane Dazzi, Alexandre Porcino, Marianna Martineau-Corcos, Charlotte Gref, Ruxandra Pharmaceutics Article Vancomycin (VCM) is a last resort antibiotic in the treatment of severe Gram-positive infections. However, its administration is limited by several drawbacks such as: strong pH-dependent charge, tendency to aggregate, low bioavailability, and poor cellular uptake. These drawbacks were circumvented by engineering pH-responsive nanoparticles (NPs) capable to incorporate high VCM payload and deliver it specifically at slightly acidic pH corresponding to infection sites. Taking advantage of peculiar physicochemical properties of VCM, here we show how to incorporate VCM efficiently in biodegradable NPs made of poly(lactic-co-glycolic acid) and polylactic acid (co)polymers. The NPs were prepared by a simple and reproducible method, establishing strong electrostatic interactions between VCM and the (co)polymers’ end groups. VCM payloads reached up to 25 wt%. The drug loading mechanism was investigated by solid state nuclear magnetic resonance spectroscopy. The engineered NPs were characterized by a set of advanced physicochemical methods, which allowed examining their morphology, internal structures, and chemical composition on an individual NP basis. The compartmentalized structure of NPs was evidenced by cryogenic transmission electronic microscopy, whereas the chemical composition of the NPs’ top layers and core was obtained by electron microscopies associated with energy-dispersive X-ray spectroscopy. Noteworthy, atomic force microscopy coupled to infrared spectroscopy allowed mapping the drug location and gave semiquantitative information about the loadings of individual NPs. In addition, the NPs were stable upon storage and did not release the incorporated drug at neutral pH. Interestingly, a slight acidification of the medium induced a rapid VCM release. The compartmentalized NPs could find potential applications for controlled VCM release at an infected site with local acidic pH. MDPI 2021-11-24 /pmc/articles/PMC8709497/ /pubmed/34959274 http://dx.doi.org/10.3390/pharmaceutics13121992 Text en © 2021 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
Ural, Merve Seray
Menéndez-Miranda, Mario
Salzano, Giuseppina
Mathurin, Jérémie
Aybeke, Ece Neslihan
Deniset-Besseau, Ariane
Dazzi, Alexandre
Porcino, Marianna
Martineau-Corcos, Charlotte
Gref, Ruxandra
Compartmentalized Polymeric Nanoparticles Deliver Vancomycin in a pH-Responsive Manner
title Compartmentalized Polymeric Nanoparticles Deliver Vancomycin in a pH-Responsive Manner
title_full Compartmentalized Polymeric Nanoparticles Deliver Vancomycin in a pH-Responsive Manner
title_fullStr Compartmentalized Polymeric Nanoparticles Deliver Vancomycin in a pH-Responsive Manner
title_full_unstemmed Compartmentalized Polymeric Nanoparticles Deliver Vancomycin in a pH-Responsive Manner
title_short Compartmentalized Polymeric Nanoparticles Deliver Vancomycin in a pH-Responsive Manner
title_sort compartmentalized polymeric nanoparticles deliver vancomycin in a ph-responsive manner
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8709497/
https://www.ncbi.nlm.nih.gov/pubmed/34959274
http://dx.doi.org/10.3390/pharmaceutics13121992
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