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Macrophage targeting of nitazoxanide-loaded transethosomal gel in cutaneous leishmaniasis
Topical delivery is preferable over systemic delivery for cutaneous leishmaniasis, because of its easy administration, reduced systemic adverse effects and low cost. Nitazoxanide (NTZ) has broad-spectrum activity against various parasites and has the potential to avoid drug resistance developed by e...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9532992/ https://www.ncbi.nlm.nih.gov/pubmed/36249328 http://dx.doi.org/10.1098/rsos.220428 |
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author | Khalid, Husna Batool, Sibgha Din, Fakhar ud Khan, Salman Khan, Gul Majid |
author_facet | Khalid, Husna Batool, Sibgha Din, Fakhar ud Khan, Salman Khan, Gul Majid |
author_sort | Khalid, Husna |
collection | PubMed |
description | Topical delivery is preferable over systemic delivery for cutaneous leishmaniasis, because of its easy administration, reduced systemic adverse effects and low cost. Nitazoxanide (NTZ) has broad-spectrum activity against various parasites and has the potential to avoid drug resistance developed by enzymatic mutations. NTZ oral formulation is associated with severe dyspepsia and stomach pain. Herein, NTZ-transethosomes (NTZ-TES) were prepared and loaded into chitosan gel (NTZ-TEG) for topical delivery. NTZ-TES were prepared by the thin-film hydration method and optimized statistically via the Box-Behnken method. The optimized formulation indicated excellent particle size (176 nm), polydispersity index (0.093), zeta potential (−26.4 mV) and entrapment efficiency (86%). The transmission electron microscopy analysis showed spherical-sized particles and Fourier-transform infrared spectroscopy analysis indicated no interaction among the excipients. Similarly, NTZ-TEG showed optimal pH, desirable viscosity and good spreadability. NTZ-TES and NTZ-TEG showed prolonged release behaviour and higher skin penetration and deposition in the epidermal/dermal layer of skin in comparison with the NTZ-dispersion. Moreover, NTZ-TES showed higher percentage inhibition, lower half-maximal inhibitory concentration (IC(50)) against promastigotes and higher macrophage uptake. Additionally, skin irritation and histopathology studies indicated the safe and non-irritant behaviour of the NTZ-TEG. The obtained findings suggested the enhanced skin permeation and improved anti-leishmanial effect of NTZ when administered as NTZ-TEG. |
format | Online Article Text |
id | pubmed-9532992 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | The Royal Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-95329922022-10-15 Macrophage targeting of nitazoxanide-loaded transethosomal gel in cutaneous leishmaniasis Khalid, Husna Batool, Sibgha Din, Fakhar ud Khan, Salman Khan, Gul Majid R Soc Open Sci Biochemistry, Cellular and Molecular Biology Topical delivery is preferable over systemic delivery for cutaneous leishmaniasis, because of its easy administration, reduced systemic adverse effects and low cost. Nitazoxanide (NTZ) has broad-spectrum activity against various parasites and has the potential to avoid drug resistance developed by enzymatic mutations. NTZ oral formulation is associated with severe dyspepsia and stomach pain. Herein, NTZ-transethosomes (NTZ-TES) were prepared and loaded into chitosan gel (NTZ-TEG) for topical delivery. NTZ-TES were prepared by the thin-film hydration method and optimized statistically via the Box-Behnken method. The optimized formulation indicated excellent particle size (176 nm), polydispersity index (0.093), zeta potential (−26.4 mV) and entrapment efficiency (86%). The transmission electron microscopy analysis showed spherical-sized particles and Fourier-transform infrared spectroscopy analysis indicated no interaction among the excipients. Similarly, NTZ-TEG showed optimal pH, desirable viscosity and good spreadability. NTZ-TES and NTZ-TEG showed prolonged release behaviour and higher skin penetration and deposition in the epidermal/dermal layer of skin in comparison with the NTZ-dispersion. Moreover, NTZ-TES showed higher percentage inhibition, lower half-maximal inhibitory concentration (IC(50)) against promastigotes and higher macrophage uptake. Additionally, skin irritation and histopathology studies indicated the safe and non-irritant behaviour of the NTZ-TEG. The obtained findings suggested the enhanced skin permeation and improved anti-leishmanial effect of NTZ when administered as NTZ-TEG. The Royal Society 2022-10-05 /pmc/articles/PMC9532992/ /pubmed/36249328 http://dx.doi.org/10.1098/rsos.220428 Text en © 2022 The Authors. https://creativecommons.org/licenses/by/4.0/Published by the Royal Society 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, provided the original author and source are credited. |
spellingShingle | Biochemistry, Cellular and Molecular Biology Khalid, Husna Batool, Sibgha Din, Fakhar ud Khan, Salman Khan, Gul Majid Macrophage targeting of nitazoxanide-loaded transethosomal gel in cutaneous leishmaniasis |
title | Macrophage targeting of nitazoxanide-loaded transethosomal gel in cutaneous leishmaniasis |
title_full | Macrophage targeting of nitazoxanide-loaded transethosomal gel in cutaneous leishmaniasis |
title_fullStr | Macrophage targeting of nitazoxanide-loaded transethosomal gel in cutaneous leishmaniasis |
title_full_unstemmed | Macrophage targeting of nitazoxanide-loaded transethosomal gel in cutaneous leishmaniasis |
title_short | Macrophage targeting of nitazoxanide-loaded transethosomal gel in cutaneous leishmaniasis |
title_sort | macrophage targeting of nitazoxanide-loaded transethosomal gel in cutaneous leishmaniasis |
topic | Biochemistry, Cellular and Molecular Biology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9532992/ https://www.ncbi.nlm.nih.gov/pubmed/36249328 http://dx.doi.org/10.1098/rsos.220428 |
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