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Oral Administration of Artemisone for the Treatment of Schistosomiasis: Formulation Challenges and In Vivo Efficacy

Artemisone is an innovative artemisinin derivative with applications in the treatment of malaria, schistosomiasis and other diseases. However, its low aqueous solubility and tendency to degrade after solubilisation limits the translation of this drug into clinical practice. We developed a self-micro...

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Autores principales: Zech, Johanna, Gold, Daniel, Salaymeh, Nadeen, Sasson, Netanel Cohen, Rabinowitch, Ithai, Golenser, Jacob, Mäder, Karsten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356104/
https://www.ncbi.nlm.nih.gov/pubmed/32503130
http://dx.doi.org/10.3390/pharmaceutics12060509
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author Zech, Johanna
Gold, Daniel
Salaymeh, Nadeen
Sasson, Netanel Cohen
Rabinowitch, Ithai
Golenser, Jacob
Mäder, Karsten
author_facet Zech, Johanna
Gold, Daniel
Salaymeh, Nadeen
Sasson, Netanel Cohen
Rabinowitch, Ithai
Golenser, Jacob
Mäder, Karsten
author_sort Zech, Johanna
collection PubMed
description Artemisone is an innovative artemisinin derivative with applications in the treatment of malaria, schistosomiasis and other diseases. However, its low aqueous solubility and tendency to degrade after solubilisation limits the translation of this drug into clinical practice. We developed a self-microemulsifying drug delivery system (SMEDDS), which is easy to produce (simple mixing) with a high drug load. In addition to known pharmaceutical excipients (Capmul MCM, Kolliphor HS15, propylene glycol), we identified Polysorb ID 46 as a beneficial new additional excipient. The physicochemical properties were characterized by dynamic light scattering, conductivity measurements, rheology and electron microscopy. High storage stability, even at 30 °C, was achieved. The orally administrated artemisone SMEDDS formulation was highly active in vivo in S. mansoni infected mice. Thorough elimination of the adult worms, their eggs and prevention of the deleterious granuloma formation in the livers of infected mice was observed even at a relatively low dose of the drug. The new formulation has a high potential to accelerate the clinical use of artemisone in schistosomiasis and malaria.
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spelling pubmed-73561042020-07-31 Oral Administration of Artemisone for the Treatment of Schistosomiasis: Formulation Challenges and In Vivo Efficacy Zech, Johanna Gold, Daniel Salaymeh, Nadeen Sasson, Netanel Cohen Rabinowitch, Ithai Golenser, Jacob Mäder, Karsten Pharmaceutics Article Artemisone is an innovative artemisinin derivative with applications in the treatment of malaria, schistosomiasis and other diseases. However, its low aqueous solubility and tendency to degrade after solubilisation limits the translation of this drug into clinical practice. We developed a self-microemulsifying drug delivery system (SMEDDS), which is easy to produce (simple mixing) with a high drug load. In addition to known pharmaceutical excipients (Capmul MCM, Kolliphor HS15, propylene glycol), we identified Polysorb ID 46 as a beneficial new additional excipient. The physicochemical properties were characterized by dynamic light scattering, conductivity measurements, rheology and electron microscopy. High storage stability, even at 30 °C, was achieved. The orally administrated artemisone SMEDDS formulation was highly active in vivo in S. mansoni infected mice. Thorough elimination of the adult worms, their eggs and prevention of the deleterious granuloma formation in the livers of infected mice was observed even at a relatively low dose of the drug. The new formulation has a high potential to accelerate the clinical use of artemisone in schistosomiasis and malaria. MDPI 2020-06-03 /pmc/articles/PMC7356104/ /pubmed/32503130 http://dx.doi.org/10.3390/pharmaceutics12060509 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zech, Johanna
Gold, Daniel
Salaymeh, Nadeen
Sasson, Netanel Cohen
Rabinowitch, Ithai
Golenser, Jacob
Mäder, Karsten
Oral Administration of Artemisone for the Treatment of Schistosomiasis: Formulation Challenges and In Vivo Efficacy
title Oral Administration of Artemisone for the Treatment of Schistosomiasis: Formulation Challenges and In Vivo Efficacy
title_full Oral Administration of Artemisone for the Treatment of Schistosomiasis: Formulation Challenges and In Vivo Efficacy
title_fullStr Oral Administration of Artemisone for the Treatment of Schistosomiasis: Formulation Challenges and In Vivo Efficacy
title_full_unstemmed Oral Administration of Artemisone for the Treatment of Schistosomiasis: Formulation Challenges and In Vivo Efficacy
title_short Oral Administration of Artemisone for the Treatment of Schistosomiasis: Formulation Challenges and In Vivo Efficacy
title_sort oral administration of artemisone for the treatment of schistosomiasis: formulation challenges and in vivo efficacy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7356104/
https://www.ncbi.nlm.nih.gov/pubmed/32503130
http://dx.doi.org/10.3390/pharmaceutics12060509
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