Polyanhydride Nanoparticle Delivery Platform Dramatically Enhances Killing of Filarial Worms.
Filarial diseases represent a significant social and economic burden to over 120 million people worldwide and are caused by endoparasites that require the presence of symbiotic bacteria of the genus Wolbachia for fertility and viability of the host parasite. Targeting Wolbachia for elimination is a...
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ftdoajarticles:oai:doaj.org/article:948d5f5acc5c4cfe82e078d67de64a18 2023-05-15T15:09:59+02:00 Polyanhydride Nanoparticle Delivery Platform Dramatically Enhances Killing of Filarial Worms. Andrea M Binnebose Shannon L Haughney Richard Martin Paula M Imerman Balaji Narasimhan Bryan H Bellaire 2015-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0004173 https://doaj.org/article/948d5f5acc5c4cfe82e078d67de64a18 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4619673?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004173 https://doaj.org/article/948d5f5acc5c4cfe82e078d67de64a18 PLoS Neglected Tropical Diseases, Vol 9, Iss 10, p e0004173 (2015) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2015 ftdoajarticles https://doi.org/10.1371/journal.pntd.0004173 2022-12-30T22:26:14Z Filarial diseases represent a significant social and economic burden to over 120 million people worldwide and are caused by endoparasites that require the presence of symbiotic bacteria of the genus Wolbachia for fertility and viability of the host parasite. Targeting Wolbachia for elimination is a therapeutic approach that shows promise in the treatment of onchocerciasis and lymphatic filariasis. Here we demonstrate the use of a biodegradable polyanhydride nanoparticle-based platform for the co-delivery of the antibiotic doxycycline with the antiparasitic drug, ivermectin, to reduce microfilarial burden and rapidly kill adult worms. When doxycycline and ivermectin were co-delivered within polyanhydride nanoparticles, effective killing of adult female Brugia malayi filarial worms was achieved with approximately 4,000-fold reduction in the amount of drug used. Additionally the time to death of the macrofilaria was also significantly reduced (five-fold) when the anti-filarial drug cocktail was delivered within polyanhydride nanoparticles. We hypothesize that the mechanism behind this dramatically enhanced killing of the macrofilaria is the ability of the polyanhydride nanoparticles to behave as a Trojan horse and penetrate the cuticle, bypassing excretory pumps of B. malayi, and effectively deliver drug directly to both the worm and Wolbachia at high enough microenvironmental concentrations to cause death. These provocative findings may have significant consequences for the reduction in the amount of drug and the length of treatment required for filarial infections in terms of patient compliance and reduced cost of treatment. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 9 10 e0004173 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
language |
English |
topic |
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 Andrea M Binnebose Shannon L Haughney Richard Martin Paula M Imerman Balaji Narasimhan Bryan H Bellaire Polyanhydride Nanoparticle Delivery Platform Dramatically Enhances Killing of Filarial Worms. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Filarial diseases represent a significant social and economic burden to over 120 million people worldwide and are caused by endoparasites that require the presence of symbiotic bacteria of the genus Wolbachia for fertility and viability of the host parasite. Targeting Wolbachia for elimination is a therapeutic approach that shows promise in the treatment of onchocerciasis and lymphatic filariasis. Here we demonstrate the use of a biodegradable polyanhydride nanoparticle-based platform for the co-delivery of the antibiotic doxycycline with the antiparasitic drug, ivermectin, to reduce microfilarial burden and rapidly kill adult worms. When doxycycline and ivermectin were co-delivered within polyanhydride nanoparticles, effective killing of adult female Brugia malayi filarial worms was achieved with approximately 4,000-fold reduction in the amount of drug used. Additionally the time to death of the macrofilaria was also significantly reduced (five-fold) when the anti-filarial drug cocktail was delivered within polyanhydride nanoparticles. We hypothesize that the mechanism behind this dramatically enhanced killing of the macrofilaria is the ability of the polyanhydride nanoparticles to behave as a Trojan horse and penetrate the cuticle, bypassing excretory pumps of B. malayi, and effectively deliver drug directly to both the worm and Wolbachia at high enough microenvironmental concentrations to cause death. These provocative findings may have significant consequences for the reduction in the amount of drug and the length of treatment required for filarial infections in terms of patient compliance and reduced cost of treatment. |
format |
Article in Journal/Newspaper |
author |
Andrea M Binnebose Shannon L Haughney Richard Martin Paula M Imerman Balaji Narasimhan Bryan H Bellaire |
author_facet |
Andrea M Binnebose Shannon L Haughney Richard Martin Paula M Imerman Balaji Narasimhan Bryan H Bellaire |
author_sort |
Andrea M Binnebose |
title |
Polyanhydride Nanoparticle Delivery Platform Dramatically Enhances Killing of Filarial Worms. |
title_short |
Polyanhydride Nanoparticle Delivery Platform Dramatically Enhances Killing of Filarial Worms. |
title_full |
Polyanhydride Nanoparticle Delivery Platform Dramatically Enhances Killing of Filarial Worms. |
title_fullStr |
Polyanhydride Nanoparticle Delivery Platform Dramatically Enhances Killing of Filarial Worms. |
title_full_unstemmed |
Polyanhydride Nanoparticle Delivery Platform Dramatically Enhances Killing of Filarial Worms. |
title_sort |
polyanhydride nanoparticle delivery platform dramatically enhances killing of filarial worms. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2015 |
url |
https://doi.org/10.1371/journal.pntd.0004173 https://doaj.org/article/948d5f5acc5c4cfe82e078d67de64a18 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 9, Iss 10, p e0004173 (2015) |
op_relation |
http://europepmc.org/articles/PMC4619673?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004173 https://doaj.org/article/948d5f5acc5c4cfe82e078d67de64a18 |
op_doi |
https://doi.org/10.1371/journal.pntd.0004173 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
9 |
container_issue |
10 |
container_start_page |
e0004173 |
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1766341074806112256 |