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A Multifunctional Polymeric Micelle for Targeted Delivery of Paclitaxel by the Inhibition of the P-Glycoprotein Transporters

P-glycoprotein (P-gP) efflux-mediated multidrug resistance is a fundamental aspect of chemotherapeutic failure in oncology. The current study aims to deliver paclitaxel (PTX) specifically at the target site with improved in vivo efficacy of poorly permeable PTX against solid tumors. Multifunctional...

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Autores principales: Razzaq, Sobia, Rauf, Aisha, Raza, Abida, Akhtar, Sohail, Tabish, Tanveer A., Sandhu, Mansur Abdullah, Zaman, Muhammad, Ibrahim, Ibrahim M., Shahnaz, Gul, Rahdar, Abbas, Díez-Pascual, Ana M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618187/
https://www.ncbi.nlm.nih.gov/pubmed/34835622
http://dx.doi.org/10.3390/nano11112858
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author Razzaq, Sobia
Rauf, Aisha
Raza, Abida
Akhtar, Sohail
Tabish, Tanveer A.
Sandhu, Mansur Abdullah
Zaman, Muhammad
Ibrahim, Ibrahim M.
Shahnaz, Gul
Rahdar, Abbas
Díez-Pascual, Ana M.
author_facet Razzaq, Sobia
Rauf, Aisha
Raza, Abida
Akhtar, Sohail
Tabish, Tanveer A.
Sandhu, Mansur Abdullah
Zaman, Muhammad
Ibrahim, Ibrahim M.
Shahnaz, Gul
Rahdar, Abbas
Díez-Pascual, Ana M.
author_sort Razzaq, Sobia
collection PubMed
description P-glycoprotein (P-gP) efflux-mediated multidrug resistance is a fundamental aspect of chemotherapeutic failure in oncology. The current study aims to deliver paclitaxel (PTX) specifically at the target site with improved in vivo efficacy of poorly permeable PTX against solid tumors. Multifunctional polymeric micelles as targeted delivery have been devised for loading and release of PTX. Mucoadhesion, permeation enhancement, oral pharmacokinetics, biodistribution, and toxicological studies were carried out to fully elucidate the therapeutic outcomes of the polymeric micelles. Ex vivo permeation studies indicated a 7.89-fold enhancement in the permeation of PTX with mucopermeating papain functionalized thiolated redox micelles (PT-R-Ms) compared to the pure PTX. Moreover, PT-R-Ms exhibited a higher percentage of apoptotic cells (42.9 ± 0.07%) compared to pure PTX. Biodistribution studies revealed that fluorotagged PT-RMs accumulated in excised tumors and organs. The higher fluorescence intensity indicated the mucopermeation of micelles across the intestine. The orally administered PT-R-Ms efficiently overcome intestinal barriers and inhibit the P-gP efflux pump, resulting in increased bioavailability of PTX (up to 8-fold) in comparison to pure PTX. The enhanced anti-tumor efficacy and reduced toxic effects are key aspects of efficient cancer therapy. This study demonstrates that the use of mucopermeating PT-R-Ms is an encouraging approach to overwhelm the permeation barrier in cancer treatment.
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spelling pubmed-86181872021-11-27 A Multifunctional Polymeric Micelle for Targeted Delivery of Paclitaxel by the Inhibition of the P-Glycoprotein Transporters Razzaq, Sobia Rauf, Aisha Raza, Abida Akhtar, Sohail Tabish, Tanveer A. Sandhu, Mansur Abdullah Zaman, Muhammad Ibrahim, Ibrahim M. Shahnaz, Gul Rahdar, Abbas Díez-Pascual, Ana M. Nanomaterials (Basel) Article P-glycoprotein (P-gP) efflux-mediated multidrug resistance is a fundamental aspect of chemotherapeutic failure in oncology. The current study aims to deliver paclitaxel (PTX) specifically at the target site with improved in vivo efficacy of poorly permeable PTX against solid tumors. Multifunctional polymeric micelles as targeted delivery have been devised for loading and release of PTX. Mucoadhesion, permeation enhancement, oral pharmacokinetics, biodistribution, and toxicological studies were carried out to fully elucidate the therapeutic outcomes of the polymeric micelles. Ex vivo permeation studies indicated a 7.89-fold enhancement in the permeation of PTX with mucopermeating papain functionalized thiolated redox micelles (PT-R-Ms) compared to the pure PTX. Moreover, PT-R-Ms exhibited a higher percentage of apoptotic cells (42.9 ± 0.07%) compared to pure PTX. Biodistribution studies revealed that fluorotagged PT-RMs accumulated in excised tumors and organs. The higher fluorescence intensity indicated the mucopermeation of micelles across the intestine. The orally administered PT-R-Ms efficiently overcome intestinal barriers and inhibit the P-gP efflux pump, resulting in increased bioavailability of PTX (up to 8-fold) in comparison to pure PTX. The enhanced anti-tumor efficacy and reduced toxic effects are key aspects of efficient cancer therapy. This study demonstrates that the use of mucopermeating PT-R-Ms is an encouraging approach to overwhelm the permeation barrier in cancer treatment. MDPI 2021-10-26 /pmc/articles/PMC8618187/ /pubmed/34835622 http://dx.doi.org/10.3390/nano11112858 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
Razzaq, Sobia
Rauf, Aisha
Raza, Abida
Akhtar, Sohail
Tabish, Tanveer A.
Sandhu, Mansur Abdullah
Zaman, Muhammad
Ibrahim, Ibrahim M.
Shahnaz, Gul
Rahdar, Abbas
Díez-Pascual, Ana M.
A Multifunctional Polymeric Micelle for Targeted Delivery of Paclitaxel by the Inhibition of the P-Glycoprotein Transporters
title A Multifunctional Polymeric Micelle for Targeted Delivery of Paclitaxel by the Inhibition of the P-Glycoprotein Transporters
title_full A Multifunctional Polymeric Micelle for Targeted Delivery of Paclitaxel by the Inhibition of the P-Glycoprotein Transporters
title_fullStr A Multifunctional Polymeric Micelle for Targeted Delivery of Paclitaxel by the Inhibition of the P-Glycoprotein Transporters
title_full_unstemmed A Multifunctional Polymeric Micelle for Targeted Delivery of Paclitaxel by the Inhibition of the P-Glycoprotein Transporters
title_short A Multifunctional Polymeric Micelle for Targeted Delivery of Paclitaxel by the Inhibition of the P-Glycoprotein Transporters
title_sort multifunctional polymeric micelle for targeted delivery of paclitaxel by the inhibition of the p-glycoprotein transporters
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8618187/
https://www.ncbi.nlm.nih.gov/pubmed/34835622
http://dx.doi.org/10.3390/nano11112858
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