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Hierarchy of the Components in Spray-Dried, Protein-Excipient Particles Using DNP-Enhanced NMR Spectroscopy

[Image: see text] Protein-based drugs are becoming increasingly important, but there are challenges associated with their formulation (for example, formulating stable inhalable aerosols while maintaining the proper long-term stability of the protein). Determining the morphology of multicomponent, pr...

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Autores principales: Berruyer, Pierrick, Lindkvist, Maria, Gracin, Sandra, Starciuc, Tatiana, Bertarello, Andrea, Busi, Baptiste, Schantz, Staffan, Emsley, Lyndon
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10630941/
https://www.ncbi.nlm.nih.gov/pubmed/37782000
http://dx.doi.org/10.1021/acs.molpharmaceut.3c00539
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author Berruyer, Pierrick
Lindkvist, Maria
Gracin, Sandra
Starciuc, Tatiana
Bertarello, Andrea
Busi, Baptiste
Schantz, Staffan
Emsley, Lyndon
author_facet Berruyer, Pierrick
Lindkvist, Maria
Gracin, Sandra
Starciuc, Tatiana
Bertarello, Andrea
Busi, Baptiste
Schantz, Staffan
Emsley, Lyndon
author_sort Berruyer, Pierrick
collection PubMed
description [Image: see text] Protein-based drugs are becoming increasingly important, but there are challenges associated with their formulation (for example, formulating stable inhalable aerosols while maintaining the proper long-term stability of the protein). Determining the morphology of multicomponent, protein-based drug formulations is particularly challenging. Here, we use dynamic nuclear polarization (DNP) solid-state NMR spectroscopy to determine the hierarchy of components within spray-dried particles containing protein, trehalose, leucine, and trileucine. DNP NMR was applied to these formulations to assess the localization of the components within the particles. We found a consistent scheme, where trehalose and the protein are co-located within the same phase in the core of the particles and leucine and trileucine are distributed in separate phases at the surface of the particles. The description of the hierarchy of the organic components determined by DNP NMR enables the rationalization of the performance of the formulation.
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spelling pubmed-106309412023-11-15 Hierarchy of the Components in Spray-Dried, Protein-Excipient Particles Using DNP-Enhanced NMR Spectroscopy Berruyer, Pierrick Lindkvist, Maria Gracin, Sandra Starciuc, Tatiana Bertarello, Andrea Busi, Baptiste Schantz, Staffan Emsley, Lyndon Mol Pharm [Image: see text] Protein-based drugs are becoming increasingly important, but there are challenges associated with their formulation (for example, formulating stable inhalable aerosols while maintaining the proper long-term stability of the protein). Determining the morphology of multicomponent, protein-based drug formulations is particularly challenging. Here, we use dynamic nuclear polarization (DNP) solid-state NMR spectroscopy to determine the hierarchy of components within spray-dried particles containing protein, trehalose, leucine, and trileucine. DNP NMR was applied to these formulations to assess the localization of the components within the particles. We found a consistent scheme, where trehalose and the protein are co-located within the same phase in the core of the particles and leucine and trileucine are distributed in separate phases at the surface of the particles. The description of the hierarchy of the organic components determined by DNP NMR enables the rationalization of the performance of the formulation. American Chemical Society 2023-10-02 /pmc/articles/PMC10630941/ /pubmed/37782000 http://dx.doi.org/10.1021/acs.molpharmaceut.3c00539 Text en © 2023 The Authors. Published by 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 Berruyer, Pierrick
Lindkvist, Maria
Gracin, Sandra
Starciuc, Tatiana
Bertarello, Andrea
Busi, Baptiste
Schantz, Staffan
Emsley, Lyndon
Hierarchy of the Components in Spray-Dried, Protein-Excipient Particles Using DNP-Enhanced NMR Spectroscopy
title Hierarchy of the Components in Spray-Dried, Protein-Excipient Particles Using DNP-Enhanced NMR Spectroscopy
title_full Hierarchy of the Components in Spray-Dried, Protein-Excipient Particles Using DNP-Enhanced NMR Spectroscopy
title_fullStr Hierarchy of the Components in Spray-Dried, Protein-Excipient Particles Using DNP-Enhanced NMR Spectroscopy
title_full_unstemmed Hierarchy of the Components in Spray-Dried, Protein-Excipient Particles Using DNP-Enhanced NMR Spectroscopy
title_short Hierarchy of the Components in Spray-Dried, Protein-Excipient Particles Using DNP-Enhanced NMR Spectroscopy
title_sort hierarchy of the components in spray-dried, protein-excipient particles using dnp-enhanced nmr spectroscopy
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10630941/
https://www.ncbi.nlm.nih.gov/pubmed/37782000
http://dx.doi.org/10.1021/acs.molpharmaceut.3c00539
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