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Dendrimer-based posaconazole nanoplatform for antifungal therapy

We examined formulating a new antifungal agent, posaconazole (POS) and its derivatives, with different molecular vehicles. Several combinations of drug and carrier molecules were synthesized, and their antifungal activities were evaluated against Aspergillus fumigatus. Posaconazole and four of its d...

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Autores principales: Tang, Shengzhuang, Chen, Jesse, Cannon, Jayme, Cao, Zhengyi, Baker, James R., Wang, Su He
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Taylor & Francis 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510609/
https://www.ncbi.nlm.nih.gov/pubmed/34617850
http://dx.doi.org/10.1080/10717544.2021.1986605
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author Tang, Shengzhuang
Chen, Jesse
Cannon, Jayme
Cao, Zhengyi
Baker, James R.
Wang, Su He
author_facet Tang, Shengzhuang
Chen, Jesse
Cannon, Jayme
Cao, Zhengyi
Baker, James R.
Wang, Su He
author_sort Tang, Shengzhuang
collection PubMed
description We examined formulating a new antifungal agent, posaconazole (POS) and its derivatives, with different molecular vehicles. Several combinations of drug and carrier molecules were synthesized, and their antifungal activities were evaluated against Aspergillus fumigatus. Posaconazole and four of its derivatives were conjugated to either generation 5 (G5) dendrimers or partially modified G5 dendrimers. The in vitro antifungal activities of these compounds suggest that conjugates with specific chemical linkages showed better fungistatic activity than direct conjugates to POS. In particular, a polyethylene glycol (PEG)-imidazole modified G5 dendrimer demonstrated improved antifungal efficacy relative to the parent G5 molecule. Further studies were then conducted with POS derived molecules coupled to PEG-imidazole modified G5 dendrimers to achieve a highly soluble and active conjugate of POS. This conjugated macromolecule averaged 23 POS molecules per G5 and had a high solubility with 50 mg/mL, which improved the molar solubility of POS from less than 0.03 mg/mL to as high as 16 mg/mL in water. The primary release profile of the drug in human plasma was extended to over 72 h, which is reflected in the in vitro inhibition of A. fumigatus growth of over 96 h. These POS–polymer conjugates appear to be novel and efficient antifungal agents.
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spelling pubmed-85106092021-10-13 Dendrimer-based posaconazole nanoplatform for antifungal therapy Tang, Shengzhuang Chen, Jesse Cannon, Jayme Cao, Zhengyi Baker, James R. Wang, Su He Drug Deliv Research Article We examined formulating a new antifungal agent, posaconazole (POS) and its derivatives, with different molecular vehicles. Several combinations of drug and carrier molecules were synthesized, and their antifungal activities were evaluated against Aspergillus fumigatus. Posaconazole and four of its derivatives were conjugated to either generation 5 (G5) dendrimers or partially modified G5 dendrimers. The in vitro antifungal activities of these compounds suggest that conjugates with specific chemical linkages showed better fungistatic activity than direct conjugates to POS. In particular, a polyethylene glycol (PEG)-imidazole modified G5 dendrimer demonstrated improved antifungal efficacy relative to the parent G5 molecule. Further studies were then conducted with POS derived molecules coupled to PEG-imidazole modified G5 dendrimers to achieve a highly soluble and active conjugate of POS. This conjugated macromolecule averaged 23 POS molecules per G5 and had a high solubility with 50 mg/mL, which improved the molar solubility of POS from less than 0.03 mg/mL to as high as 16 mg/mL in water. The primary release profile of the drug in human plasma was extended to over 72 h, which is reflected in the in vitro inhibition of A. fumigatus growth of over 96 h. These POS–polymer conjugates appear to be novel and efficient antifungal agents. Taylor & Francis 2021-10-07 /pmc/articles/PMC8510609/ /pubmed/34617850 http://dx.doi.org/10.1080/10717544.2021.1986605 Text en © 2021 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Tang, Shengzhuang
Chen, Jesse
Cannon, Jayme
Cao, Zhengyi
Baker, James R.
Wang, Su He
Dendrimer-based posaconazole nanoplatform for antifungal therapy
title Dendrimer-based posaconazole nanoplatform for antifungal therapy
title_full Dendrimer-based posaconazole nanoplatform for antifungal therapy
title_fullStr Dendrimer-based posaconazole nanoplatform for antifungal therapy
title_full_unstemmed Dendrimer-based posaconazole nanoplatform for antifungal therapy
title_short Dendrimer-based posaconazole nanoplatform for antifungal therapy
title_sort dendrimer-based posaconazole nanoplatform for antifungal therapy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8510609/
https://www.ncbi.nlm.nih.gov/pubmed/34617850
http://dx.doi.org/10.1080/10717544.2021.1986605
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