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Polymer Microparticles Prolong Delivery of the 15-PGDH Inhibitor SW033291

As the prevalence of age-related fibrotic diseases continues to increase, novel antifibrotic therapies are emerging to address clinical needs. However, many novel therapeutics for managing chronic fibrosis are small-molecule drugs that require frequent dosing to attain effective concentrations. Alth...

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Autores principales: Dogan, Alan B., Rohner, Nathan A., Smith, Julianne N. P., Kilgore, Jessica A., Williams, Noelle S., Markowitz, Sanford D., von Recum, Horst A., Desai, Amar B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779392/
https://www.ncbi.nlm.nih.gov/pubmed/35056981
http://dx.doi.org/10.3390/pharmaceutics14010085
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author Dogan, Alan B.
Rohner, Nathan A.
Smith, Julianne N. P.
Kilgore, Jessica A.
Williams, Noelle S.
Markowitz, Sanford D.
von Recum, Horst A.
Desai, Amar B.
author_facet Dogan, Alan B.
Rohner, Nathan A.
Smith, Julianne N. P.
Kilgore, Jessica A.
Williams, Noelle S.
Markowitz, Sanford D.
von Recum, Horst A.
Desai, Amar B.
author_sort Dogan, Alan B.
collection PubMed
description As the prevalence of age-related fibrotic diseases continues to increase, novel antifibrotic therapies are emerging to address clinical needs. However, many novel therapeutics for managing chronic fibrosis are small-molecule drugs that require frequent dosing to attain effective concentrations. Although bolus parenteral administrations have become standard clinical practice, an extended delivery platform would achieve steady-state concentrations over a longer time period with fewer administrations. This study lays the foundation for the development of a sustained release platform for the delivery of (+)SW033291, a potent, small-molecule inhibitor of the 15-hydroxyprostaglandin dehydrogenase (15-PGDH) enzyme, which has previously demonstrated efficacy in a murine model of pulmonary fibrosis. Herein, we leverage fine-tuned cyclodextrin microparticles—specifically, β-CD microparticles (β-CD MPs)—to extend the delivery of the 15-PGDH inhibitor, (+)SW033291, to over one week.
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spelling pubmed-87793922022-01-22 Polymer Microparticles Prolong Delivery of the 15-PGDH Inhibitor SW033291 Dogan, Alan B. Rohner, Nathan A. Smith, Julianne N. P. Kilgore, Jessica A. Williams, Noelle S. Markowitz, Sanford D. von Recum, Horst A. Desai, Amar B. Pharmaceutics Article As the prevalence of age-related fibrotic diseases continues to increase, novel antifibrotic therapies are emerging to address clinical needs. However, many novel therapeutics for managing chronic fibrosis are small-molecule drugs that require frequent dosing to attain effective concentrations. Although bolus parenteral administrations have become standard clinical practice, an extended delivery platform would achieve steady-state concentrations over a longer time period with fewer administrations. This study lays the foundation for the development of a sustained release platform for the delivery of (+)SW033291, a potent, small-molecule inhibitor of the 15-hydroxyprostaglandin dehydrogenase (15-PGDH) enzyme, which has previously demonstrated efficacy in a murine model of pulmonary fibrosis. Herein, we leverage fine-tuned cyclodextrin microparticles—specifically, β-CD microparticles (β-CD MPs)—to extend the delivery of the 15-PGDH inhibitor, (+)SW033291, to over one week. MDPI 2021-12-30 /pmc/articles/PMC8779392/ /pubmed/35056981 http://dx.doi.org/10.3390/pharmaceutics14010085 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
Dogan, Alan B.
Rohner, Nathan A.
Smith, Julianne N. P.
Kilgore, Jessica A.
Williams, Noelle S.
Markowitz, Sanford D.
von Recum, Horst A.
Desai, Amar B.
Polymer Microparticles Prolong Delivery of the 15-PGDH Inhibitor SW033291
title Polymer Microparticles Prolong Delivery of the 15-PGDH Inhibitor SW033291
title_full Polymer Microparticles Prolong Delivery of the 15-PGDH Inhibitor SW033291
title_fullStr Polymer Microparticles Prolong Delivery of the 15-PGDH Inhibitor SW033291
title_full_unstemmed Polymer Microparticles Prolong Delivery of the 15-PGDH Inhibitor SW033291
title_short Polymer Microparticles Prolong Delivery of the 15-PGDH Inhibitor SW033291
title_sort polymer microparticles prolong delivery of the 15-pgdh inhibitor sw033291
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8779392/
https://www.ncbi.nlm.nih.gov/pubmed/35056981
http://dx.doi.org/10.3390/pharmaceutics14010085
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