Improvement of Antialveolar echinococcosis efficacy of novel Albendazole-Bile acids Derivatives with Enhanced Oral Bioavailability.
Alveolar echinococcosis (AE) is a chronic and fatal infectious parasitic disease, which has not been well-researched. Current recommended therapies for AE by the World Health Organization include complete removal of the infected tissue followed by two years of albendazole (ABZ), administered orally,...
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ftdoajarticles:oai:doaj.org/article:4291dc35e225408e9c77587377a4bae7 2023-05-15T15:15:08+02:00 Improvement of Antialveolar echinococcosis efficacy of novel Albendazole-Bile acids Derivatives with Enhanced Oral Bioavailability. Chunhui Hu Meng Qin Fabin Zhang Ruixue Gao Xuehui Gan Tao Du 2023-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0011031 https://doaj.org/article/4291dc35e225408e9c77587377a4bae7 EN eng Public Library of Science (PLoS) https://doi.org/10.1371/journal.pntd.0011031 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0011031 https://doaj.org/article/4291dc35e225408e9c77587377a4bae7 PLoS Neglected Tropical Diseases, Vol 17, Iss 1, p e0011031 (2023) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2023 ftdoajarticles https://doi.org/10.1371/journal.pntd.0011031 2023-03-05T01:33:15Z Alveolar echinococcosis (AE) is a chronic and fatal infectious parasitic disease, which has not been well-researched. Current recommended therapies for AE by the World Health Organization include complete removal of the infected tissue followed by two years of albendazole (ABZ), administered orally, which is the only effective first-line anti-AE drug. Unfortunately, in most cases, complete resection of AE lesions is impossible, requiring ABZ administration for even longer periods. Only one-third of patients experienced complete remission or cure with such treatments, primarily due to ABZ's low solubility and low bioavailability. To improve ABZ bioavailability, albendazole bile acid derivative (ABZ-BA) has been designed and synthesized. Its structure was identified by mass spectrometry and nuclear magnetic resonance. Its physicochemical properties were evaluated by wide-angle X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and polarizing microscopy; it was compared with ABZ to assess its solubilization mechanism at the molecular level. To avoid the effects of bile acid on the efficacy of albendazole, the inhibitory effect of ABZ-BA on protoscolex (PSCs)s was observed in vitro. The inhibitory effect of ABZ-BA on PSCs was evaluated by survival rate, ultrastructural changes, and the expression of key cytokines during PSC apoptosis. The results showed that ABZ-BA with 4-amino-1-butanol as a linker was successfully prepared. Physicochemical characterization demonstrated that the molecular arrangement of ABZ-BA presents a short-range disordered amorphous state, which changes the drug morphology compared with crystalline ABZ. The equilibrium solubility of ABZ-BA was 4-fold higher than ABZ in vitro. ABZ-BA relative bioavailability (Frel) in Sprague-Dawley (SD) rats was 26-fold higher than ABZ in vivo. The inhibitory effect of ABZ-BA on PSCs was identical to that of ABZ, indicating that adding bile acid did not affect the efficacy of anti-echinococcosis. In the pharmacodynamics study, ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 17 1 e0011031 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Chunhui Hu Meng Qin Fabin Zhang Ruixue Gao Xuehui Gan Tao Du Improvement of Antialveolar echinococcosis efficacy of novel Albendazole-Bile acids Derivatives with Enhanced Oral Bioavailability. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Alveolar echinococcosis (AE) is a chronic and fatal infectious parasitic disease, which has not been well-researched. Current recommended therapies for AE by the World Health Organization include complete removal of the infected tissue followed by two years of albendazole (ABZ), administered orally, which is the only effective first-line anti-AE drug. Unfortunately, in most cases, complete resection of AE lesions is impossible, requiring ABZ administration for even longer periods. Only one-third of patients experienced complete remission or cure with such treatments, primarily due to ABZ's low solubility and low bioavailability. To improve ABZ bioavailability, albendazole bile acid derivative (ABZ-BA) has been designed and synthesized. Its structure was identified by mass spectrometry and nuclear magnetic resonance. Its physicochemical properties were evaluated by wide-angle X-ray diffraction, differential scanning calorimetry, scanning electron microscopy, and polarizing microscopy; it was compared with ABZ to assess its solubilization mechanism at the molecular level. To avoid the effects of bile acid on the efficacy of albendazole, the inhibitory effect of ABZ-BA on protoscolex (PSCs)s was observed in vitro. The inhibitory effect of ABZ-BA on PSCs was evaluated by survival rate, ultrastructural changes, and the expression of key cytokines during PSC apoptosis. The results showed that ABZ-BA with 4-amino-1-butanol as a linker was successfully prepared. Physicochemical characterization demonstrated that the molecular arrangement of ABZ-BA presents a short-range disordered amorphous state, which changes the drug morphology compared with crystalline ABZ. The equilibrium solubility of ABZ-BA was 4-fold higher than ABZ in vitro. ABZ-BA relative bioavailability (Frel) in Sprague-Dawley (SD) rats was 26-fold higher than ABZ in vivo. The inhibitory effect of ABZ-BA on PSCs was identical to that of ABZ, indicating that adding bile acid did not affect the efficacy of anti-echinococcosis. In the pharmacodynamics study, ... |
format |
Article in Journal/Newspaper |
author |
Chunhui Hu Meng Qin Fabin Zhang Ruixue Gao Xuehui Gan Tao Du |
author_facet |
Chunhui Hu Meng Qin Fabin Zhang Ruixue Gao Xuehui Gan Tao Du |
author_sort |
Chunhui Hu |
title |
Improvement of Antialveolar echinococcosis efficacy of novel Albendazole-Bile acids Derivatives with Enhanced Oral Bioavailability. |
title_short |
Improvement of Antialveolar echinococcosis efficacy of novel Albendazole-Bile acids Derivatives with Enhanced Oral Bioavailability. |
title_full |
Improvement of Antialveolar echinococcosis efficacy of novel Albendazole-Bile acids Derivatives with Enhanced Oral Bioavailability. |
title_fullStr |
Improvement of Antialveolar echinococcosis efficacy of novel Albendazole-Bile acids Derivatives with Enhanced Oral Bioavailability. |
title_full_unstemmed |
Improvement of Antialveolar echinococcosis efficacy of novel Albendazole-Bile acids Derivatives with Enhanced Oral Bioavailability. |
title_sort |
improvement of antialveolar echinococcosis efficacy of novel albendazole-bile acids derivatives with enhanced oral bioavailability. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2023 |
url |
https://doi.org/10.1371/journal.pntd.0011031 https://doaj.org/article/4291dc35e225408e9c77587377a4bae7 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 17, Iss 1, p e0011031 (2023) |
op_relation |
https://doi.org/10.1371/journal.pntd.0011031 https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0011031 https://doaj.org/article/4291dc35e225408e9c77587377a4bae7 |
op_doi |
https://doi.org/10.1371/journal.pntd.0011031 |
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PLOS Neglected Tropical Diseases |
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17 |
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1 |
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e0011031 |
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1766345515137499136 |