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Patterned Drug-Eluting Coatings for Tracheal Stents Based on PLA, PLGA, and PCL for the Granulation Formation Reduction: In Vivo Studies

Expandable metallic stent placement is often the only way to treat airway obstructions. Such treatment with an uncoated stent causes granulation proliferation and subsequent restenosis, resulting in the procedure’s adverse complications. Systemic administration of steroids drugs in high dosages slow...

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Autores principales: Sindeeva, Olga A., Prikhozhdenko, Ekaterina S., Schurov, Igor, Sedykh, Nikolay, Goriainov, Sergey, Karamyan, Arfenya, Mordovina, Ekaterina A., Inozemtseva, Olga A., Kudryavtseva, Valeriya, Shchesnyak, Leonid E., Abramovich, Rimma A., Mikhajlov, Sergey, Sukhorukov, Gleb B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469052/
https://www.ncbi.nlm.nih.gov/pubmed/34575513
http://dx.doi.org/10.3390/pharmaceutics13091437
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author Sindeeva, Olga A.
Prikhozhdenko, Ekaterina S.
Schurov, Igor
Sedykh, Nikolay
Goriainov, Sergey
Karamyan, Arfenya
Mordovina, Ekaterina A.
Inozemtseva, Olga A.
Kudryavtseva, Valeriya
Shchesnyak, Leonid E.
Abramovich, Rimma A.
Mikhajlov, Sergey
Sukhorukov, Gleb B.
author_facet Sindeeva, Olga A.
Prikhozhdenko, Ekaterina S.
Schurov, Igor
Sedykh, Nikolay
Goriainov, Sergey
Karamyan, Arfenya
Mordovina, Ekaterina A.
Inozemtseva, Olga A.
Kudryavtseva, Valeriya
Shchesnyak, Leonid E.
Abramovich, Rimma A.
Mikhajlov, Sergey
Sukhorukov, Gleb B.
author_sort Sindeeva, Olga A.
collection PubMed
description Expandable metallic stent placement is often the only way to treat airway obstructions. Such treatment with an uncoated stent causes granulation proliferation and subsequent restenosis, resulting in the procedure’s adverse complications. Systemic administration of steroids drugs in high dosages slows down granulation tissue overgrowth but leads to long-term side effects. Drug-eluting coatings have been used widely in cardiology for many years to suppress local granulation and reduce the organism’s systemic load. Still, so far, there are no available analogs for the trachea. Here, we demonstrate that PLA-, PCL- and PLGA-based films with arrays of microchambers to accommodate therapeutic substances can be used as a drug-eluting coating through securely fixing on the surface of an expandable nitinol stent. PCL and PLA were most resistant to mechanical damage associated with packing in delivery devices and making it possible to keep high-molecular-weight cargo. Low-molecular-weight methylprednisolone sodium succinate is poorly retained in PCL- and PLGA-based microchambers after immersion in deionized water (only 9.5% and 15.7% are left, respectively). In comparison, PLA-based microchambers retain 96.3% after the same procedure. In vivo studies on rabbits have shown that effective granulation tissue suppression is achieved when PLA and PLGA are used for coatings. PLGA-based microchamber coating almost completely degrades in 10 days in the trachea, while PLA-based microchamber films partially preserve their structure. The PCL-based film coating is most stable over time, which probably causes blocking the outflow of fluid from the tracheal mucosa and the aggravation of the inflammatory process against the background of low drug concentration. Combination and variability of polymers in the fabrication of films with microchambers to retain therapeutic compounds are suggested as a novel type of drug-eluting coating.
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spelling pubmed-84690522021-09-27 Patterned Drug-Eluting Coatings for Tracheal Stents Based on PLA, PLGA, and PCL for the Granulation Formation Reduction: In Vivo Studies Sindeeva, Olga A. Prikhozhdenko, Ekaterina S. Schurov, Igor Sedykh, Nikolay Goriainov, Sergey Karamyan, Arfenya Mordovina, Ekaterina A. Inozemtseva, Olga A. Kudryavtseva, Valeriya Shchesnyak, Leonid E. Abramovich, Rimma A. Mikhajlov, Sergey Sukhorukov, Gleb B. Pharmaceutics Article Expandable metallic stent placement is often the only way to treat airway obstructions. Such treatment with an uncoated stent causes granulation proliferation and subsequent restenosis, resulting in the procedure’s adverse complications. Systemic administration of steroids drugs in high dosages slows down granulation tissue overgrowth but leads to long-term side effects. Drug-eluting coatings have been used widely in cardiology for many years to suppress local granulation and reduce the organism’s systemic load. Still, so far, there are no available analogs for the trachea. Here, we demonstrate that PLA-, PCL- and PLGA-based films with arrays of microchambers to accommodate therapeutic substances can be used as a drug-eluting coating through securely fixing on the surface of an expandable nitinol stent. PCL and PLA were most resistant to mechanical damage associated with packing in delivery devices and making it possible to keep high-molecular-weight cargo. Low-molecular-weight methylprednisolone sodium succinate is poorly retained in PCL- and PLGA-based microchambers after immersion in deionized water (only 9.5% and 15.7% are left, respectively). In comparison, PLA-based microchambers retain 96.3% after the same procedure. In vivo studies on rabbits have shown that effective granulation tissue suppression is achieved when PLA and PLGA are used for coatings. PLGA-based microchamber coating almost completely degrades in 10 days in the trachea, while PLA-based microchamber films partially preserve their structure. The PCL-based film coating is most stable over time, which probably causes blocking the outflow of fluid from the tracheal mucosa and the aggravation of the inflammatory process against the background of low drug concentration. Combination and variability of polymers in the fabrication of films with microchambers to retain therapeutic compounds are suggested as a novel type of drug-eluting coating. MDPI 2021-09-09 /pmc/articles/PMC8469052/ /pubmed/34575513 http://dx.doi.org/10.3390/pharmaceutics13091437 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
Sindeeva, Olga A.
Prikhozhdenko, Ekaterina S.
Schurov, Igor
Sedykh, Nikolay
Goriainov, Sergey
Karamyan, Arfenya
Mordovina, Ekaterina A.
Inozemtseva, Olga A.
Kudryavtseva, Valeriya
Shchesnyak, Leonid E.
Abramovich, Rimma A.
Mikhajlov, Sergey
Sukhorukov, Gleb B.
Patterned Drug-Eluting Coatings for Tracheal Stents Based on PLA, PLGA, and PCL for the Granulation Formation Reduction: In Vivo Studies
title Patterned Drug-Eluting Coatings for Tracheal Stents Based on PLA, PLGA, and PCL for the Granulation Formation Reduction: In Vivo Studies
title_full Patterned Drug-Eluting Coatings for Tracheal Stents Based on PLA, PLGA, and PCL for the Granulation Formation Reduction: In Vivo Studies
title_fullStr Patterned Drug-Eluting Coatings for Tracheal Stents Based on PLA, PLGA, and PCL for the Granulation Formation Reduction: In Vivo Studies
title_full_unstemmed Patterned Drug-Eluting Coatings for Tracheal Stents Based on PLA, PLGA, and PCL for the Granulation Formation Reduction: In Vivo Studies
title_short Patterned Drug-Eluting Coatings for Tracheal Stents Based on PLA, PLGA, and PCL for the Granulation Formation Reduction: In Vivo Studies
title_sort patterned drug-eluting coatings for tracheal stents based on pla, plga, and pcl for the granulation formation reduction: in vivo studies
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8469052/
https://www.ncbi.nlm.nih.gov/pubmed/34575513
http://dx.doi.org/10.3390/pharmaceutics13091437
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