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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...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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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. |
format | Online Article Text |
id | pubmed-8618187 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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