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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Chemical Society
2023
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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. |
format | Online Article Text |
id | pubmed-10630941 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | American Chemical Society |
record_format | MEDLINE/PubMed |
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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