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Brain targeting of zolmitriptan via transdermal terpesomes: statistical optimization and in vivo biodistribution study by (99m)Tc radiolabeling technique
Zolmitriptan (ZT) is a potent second generation triptan, commonly administered to alleviate migraine attacks. ZT suffers various limitations; massive hepatic first pass metabolism, P-gp efflux transporters susceptibility, and limited (≈40%) oral bioavailability. Transdermal route of administration c...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer US
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10624728/ https://www.ncbi.nlm.nih.gov/pubmed/37273147 http://dx.doi.org/10.1007/s13346-023-01373-0 |
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author | Tawfik, Mai Ahmed Eltaweel, Mai M. Fatouh, Ahmed M. Shamsel-Din, Hesham A. Ibrahim, Ahmed B. |
author_facet | Tawfik, Mai Ahmed Eltaweel, Mai M. Fatouh, Ahmed M. Shamsel-Din, Hesham A. Ibrahim, Ahmed B. |
author_sort | Tawfik, Mai Ahmed |
collection | PubMed |
description | Zolmitriptan (ZT) is a potent second generation triptan, commonly administered to alleviate migraine attacks. ZT suffers various limitations; massive hepatic first pass metabolism, P-gp efflux transporters susceptibility, and limited (≈40%) oral bioavailability. Transdermal route of administration could be explored to enhance its bioavailability. A 2(3).3(1) full factorial design was constructed to developed twenty-four ZT loaded terpesomes via thin film hydration technique. The influence of drug: phosphatidylcholine ratio, terpene type, terpene concentration and sodium deoxycholate concentration on the characterization of the developed ZT-loaded terpesomes was assessed. Particle size (PS), zeta potential (ZP), ZT entrapment efficiency (EE%), drug loading (DL%) and drug released percentages after 6 h (Q(6h)) were the selected dependent variables. Further morphological, crystallinity, and in-vivo histopathological studies were conducted for the optimum terpesomes (T6). (99m)Tc-ZT and (99m)Tc-ZT-T6 gel were radio-formulated for in-vivo biodistribution studies in mice following transdermal application of (99m)Tc-ZT-T6 gel, relative to (99m)Tc-ZT oral solution. T6 terpesomes [comprising ZT and phosphatidylcholine (1:15), cineole (1% w/v) and sodium deoxycholate (0.1% w/v)] were optimum with respect to spherical PS (290.2 nm), ZP (-48.9 mV), EE% (83%), DL% (3.9%) and Q(6h) (92.2%) with desirability value of 0.85. The safety of the developed T6 terpesomes was verified by the in-vivo histopathological studies. (99m)Tc-ZT-T6 gel showed maximum brain concentration (5 ± 0.1%ID/ g) with highest brain to blood ratio of 1.92 ± 0.1 at 4 h post transdermal application. Significant improvement of ZT brain relative bioavailability (529%) and high brain targeting efficiency (315%) were revealed with (99m)Tc-ZT-T6 gel, which confirmed successful ZT delivery to the brain. Terpesomes could be safe, successful systems capable of improving ZT bioavailability with high brain targeting efficiency. GRAPHICAL ABSTRACT: [Image: see text] |
format | Online Article Text |
id | pubmed-10624728 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Springer US |
record_format | MEDLINE/PubMed |
spelling | pubmed-106247282023-11-05 Brain targeting of zolmitriptan via transdermal terpesomes: statistical optimization and in vivo biodistribution study by (99m)Tc radiolabeling technique Tawfik, Mai Ahmed Eltaweel, Mai M. Fatouh, Ahmed M. Shamsel-Din, Hesham A. Ibrahim, Ahmed B. Drug Deliv Transl Res Original Article Zolmitriptan (ZT) is a potent second generation triptan, commonly administered to alleviate migraine attacks. ZT suffers various limitations; massive hepatic first pass metabolism, P-gp efflux transporters susceptibility, and limited (≈40%) oral bioavailability. Transdermal route of administration could be explored to enhance its bioavailability. A 2(3).3(1) full factorial design was constructed to developed twenty-four ZT loaded terpesomes via thin film hydration technique. The influence of drug: phosphatidylcholine ratio, terpene type, terpene concentration and sodium deoxycholate concentration on the characterization of the developed ZT-loaded terpesomes was assessed. Particle size (PS), zeta potential (ZP), ZT entrapment efficiency (EE%), drug loading (DL%) and drug released percentages after 6 h (Q(6h)) were the selected dependent variables. Further morphological, crystallinity, and in-vivo histopathological studies were conducted for the optimum terpesomes (T6). (99m)Tc-ZT and (99m)Tc-ZT-T6 gel were radio-formulated for in-vivo biodistribution studies in mice following transdermal application of (99m)Tc-ZT-T6 gel, relative to (99m)Tc-ZT oral solution. T6 terpesomes [comprising ZT and phosphatidylcholine (1:15), cineole (1% w/v) and sodium deoxycholate (0.1% w/v)] were optimum with respect to spherical PS (290.2 nm), ZP (-48.9 mV), EE% (83%), DL% (3.9%) and Q(6h) (92.2%) with desirability value of 0.85. The safety of the developed T6 terpesomes was verified by the in-vivo histopathological studies. (99m)Tc-ZT-T6 gel showed maximum brain concentration (5 ± 0.1%ID/ g) with highest brain to blood ratio of 1.92 ± 0.1 at 4 h post transdermal application. Significant improvement of ZT brain relative bioavailability (529%) and high brain targeting efficiency (315%) were revealed with (99m)Tc-ZT-T6 gel, which confirmed successful ZT delivery to the brain. Terpesomes could be safe, successful systems capable of improving ZT bioavailability with high brain targeting efficiency. GRAPHICAL ABSTRACT: [Image: see text] Springer US 2023-06-05 2023 /pmc/articles/PMC10624728/ /pubmed/37273147 http://dx.doi.org/10.1007/s13346-023-01373-0 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Article Tawfik, Mai Ahmed Eltaweel, Mai M. Fatouh, Ahmed M. Shamsel-Din, Hesham A. Ibrahim, Ahmed B. Brain targeting of zolmitriptan via transdermal terpesomes: statistical optimization and in vivo biodistribution study by (99m)Tc radiolabeling technique |
title | Brain targeting of zolmitriptan via transdermal terpesomes: statistical optimization and in vivo biodistribution study by (99m)Tc radiolabeling technique |
title_full | Brain targeting of zolmitriptan via transdermal terpesomes: statistical optimization and in vivo biodistribution study by (99m)Tc radiolabeling technique |
title_fullStr | Brain targeting of zolmitriptan via transdermal terpesomes: statistical optimization and in vivo biodistribution study by (99m)Tc radiolabeling technique |
title_full_unstemmed | Brain targeting of zolmitriptan via transdermal terpesomes: statistical optimization and in vivo biodistribution study by (99m)Tc radiolabeling technique |
title_short | Brain targeting of zolmitriptan via transdermal terpesomes: statistical optimization and in vivo biodistribution study by (99m)Tc radiolabeling technique |
title_sort | brain targeting of zolmitriptan via transdermal terpesomes: statistical optimization and in vivo biodistribution study by (99m)tc radiolabeling technique |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10624728/ https://www.ncbi.nlm.nih.gov/pubmed/37273147 http://dx.doi.org/10.1007/s13346-023-01373-0 |
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