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Film-Forming Systems for the Delivery of DNDI-0690 to Treat Cutaneous Leishmaniasis

In cutaneous leishmaniasis (CL), parasites reside in the dermis, creating an opportunity for local drug administration potentially reducing adverse effects and improving treatment adherence compared to current therapies. Polymeric film-forming systems (FFSs) are directly applied to the skin and form...

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Autores principales: Van Bocxlaer, Katrien, McArthur, Kerri-Nicola, Harris, Andy, Alavijeh, Mo, Braillard, Stéphanie, Mowbray, Charles E., Croft, Simon L.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069359/
https://www.ncbi.nlm.nih.gov/pubmed/33918099
http://dx.doi.org/10.3390/pharmaceutics13040516
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author Van Bocxlaer, Katrien
McArthur, Kerri-Nicola
Harris, Andy
Alavijeh, Mo
Braillard, Stéphanie
Mowbray, Charles E.
Croft, Simon L.
author_facet Van Bocxlaer, Katrien
McArthur, Kerri-Nicola
Harris, Andy
Alavijeh, Mo
Braillard, Stéphanie
Mowbray, Charles E.
Croft, Simon L.
author_sort Van Bocxlaer, Katrien
collection PubMed
description In cutaneous leishmaniasis (CL), parasites reside in the dermis, creating an opportunity for local drug administration potentially reducing adverse effects and improving treatment adherence compared to current therapies. Polymeric film-forming systems (FFSs) are directly applied to the skin and form a thin film as the solvent evaporates. In contrast to conventional topical dosage forms, FFSs strongly adhere to the skin, favouring sustained drug delivery to the affected site, reducing the need for frequent applications, and enhancing patient compliance. This study reports the first investigation of the use of film-forming systems for the delivery of DNDI-0690, a nitroimidazole compound with potent activity against CL-causing Leishmania species. A total of seven polymers with or without plasticiser were evaluated for drying time, stickiness, film-flexibility, and cosmetic attributes; three FFSs yielded a positive evaluation for all test parameters. The impact of each of these FFSs on the permeation of the model skin permeant hydrocortisone (hydrocortisone, 1% (w/v) across the Strat-M membrane was evaluated, and the formulations resulting in the highest and lowest permeation flux (Klucel LF with triethyl citrate and Eudragit RS with dibutyl sebacate, respectively) were selected as the FFS vehicle for DNDI-0690. The release and skin distribution of the drug upon application to Leishmania-infected and uninfected BALB/c mouse skin were examined using Franz diffusion cells followed by an evaluation of the efficacy of both DNDI-0690 FFSs (1% (w/v)) in an experimental CL model. Whereas the Eudragit film resulted in a higher permeation of DNDI-0690, the Klucel film was able to deposit four times more drug into the skin, where the parasite resides. Of the FFSs formulations, only the Eudragit system resulted in a reduced parasite load, but not reduced lesion size, when compared to the vehicle only control. Whereas drug delivery into the skin was successfully modulated using different FFS systems, the FFS systems selected were not effective for the topical application of DNDI-0690. The convenience and aesthetic of FFS systems alongside their ability to modulate drug delivery to and into the skin merit further investigation using other promising antileishmanial drugs.
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spelling pubmed-80693592021-04-26 Film-Forming Systems for the Delivery of DNDI-0690 to Treat Cutaneous Leishmaniasis Van Bocxlaer, Katrien McArthur, Kerri-Nicola Harris, Andy Alavijeh, Mo Braillard, Stéphanie Mowbray, Charles E. Croft, Simon L. Pharmaceutics Article In cutaneous leishmaniasis (CL), parasites reside in the dermis, creating an opportunity for local drug administration potentially reducing adverse effects and improving treatment adherence compared to current therapies. Polymeric film-forming systems (FFSs) are directly applied to the skin and form a thin film as the solvent evaporates. In contrast to conventional topical dosage forms, FFSs strongly adhere to the skin, favouring sustained drug delivery to the affected site, reducing the need for frequent applications, and enhancing patient compliance. This study reports the first investigation of the use of film-forming systems for the delivery of DNDI-0690, a nitroimidazole compound with potent activity against CL-causing Leishmania species. A total of seven polymers with or without plasticiser were evaluated for drying time, stickiness, film-flexibility, and cosmetic attributes; three FFSs yielded a positive evaluation for all test parameters. The impact of each of these FFSs on the permeation of the model skin permeant hydrocortisone (hydrocortisone, 1% (w/v) across the Strat-M membrane was evaluated, and the formulations resulting in the highest and lowest permeation flux (Klucel LF with triethyl citrate and Eudragit RS with dibutyl sebacate, respectively) were selected as the FFS vehicle for DNDI-0690. The release and skin distribution of the drug upon application to Leishmania-infected and uninfected BALB/c mouse skin were examined using Franz diffusion cells followed by an evaluation of the efficacy of both DNDI-0690 FFSs (1% (w/v)) in an experimental CL model. Whereas the Eudragit film resulted in a higher permeation of DNDI-0690, the Klucel film was able to deposit four times more drug into the skin, where the parasite resides. Of the FFSs formulations, only the Eudragit system resulted in a reduced parasite load, but not reduced lesion size, when compared to the vehicle only control. Whereas drug delivery into the skin was successfully modulated using different FFS systems, the FFS systems selected were not effective for the topical application of DNDI-0690. The convenience and aesthetic of FFS systems alongside their ability to modulate drug delivery to and into the skin merit further investigation using other promising antileishmanial drugs. MDPI 2021-04-08 /pmc/articles/PMC8069359/ /pubmed/33918099 http://dx.doi.org/10.3390/pharmaceutics13040516 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
Van Bocxlaer, Katrien
McArthur, Kerri-Nicola
Harris, Andy
Alavijeh, Mo
Braillard, Stéphanie
Mowbray, Charles E.
Croft, Simon L.
Film-Forming Systems for the Delivery of DNDI-0690 to Treat Cutaneous Leishmaniasis
title Film-Forming Systems for the Delivery of DNDI-0690 to Treat Cutaneous Leishmaniasis
title_full Film-Forming Systems for the Delivery of DNDI-0690 to Treat Cutaneous Leishmaniasis
title_fullStr Film-Forming Systems for the Delivery of DNDI-0690 to Treat Cutaneous Leishmaniasis
title_full_unstemmed Film-Forming Systems for the Delivery of DNDI-0690 to Treat Cutaneous Leishmaniasis
title_short Film-Forming Systems for the Delivery of DNDI-0690 to Treat Cutaneous Leishmaniasis
title_sort film-forming systems for the delivery of dndi-0690 to treat cutaneous leishmaniasis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8069359/
https://www.ncbi.nlm.nih.gov/pubmed/33918099
http://dx.doi.org/10.3390/pharmaceutics13040516
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