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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sobia Razzaq, Aisha Rauf, Abida Raza, Sohail Akhtar, Tanveer A. Tabish, Mansur Abdullah Sandhu, Muhammad Zaman, Ibrahim M. Ibrahim, Gul Shahnaz, Abbas Rahdar, Ana M. Díez-Pascual
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	P-gP efflux biodistribution mucoadhesion resistance fluorescent micelles Chemistry QD1-999
Acceso en línea:	https://doaj.org/article/5392668d811a4f03bcf1fa7882ced679
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:5392668d811a4f03bcf1fa7882ced679
record_format	dspace
spelling	oai:doaj.org-article:5392668d811a4f03bcf1fa7882ced6792021-11-25T18:30:24ZA Multifunctional Polymeric Micelle for Targeted Delivery of Paclitaxel by the Inhibition of the P-Glycoprotein Transporters10.3390/nano111128582079-4991https://doaj.org/article/5392668d811a4f03bcf1fa7882ced6792021-10-01T00:00:00Zhttps://www.mdpi.com/2079-4991/11/11/2858https://doaj.org/toc/2079-4991P-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.Sobia RazzaqAisha RaufAbida RazaSohail AkhtarTanveer A. TabishMansur Abdullah SandhuMuhammad ZamanIbrahim M. IbrahimGul ShahnazAbbas RahdarAna M. Díez-PascualMDPI AGarticleP-gP effluxbiodistributionmucoadhesionresistancefluorescent micellesChemistryQD1-999ENNanomaterials, Vol 11, Iss 2858, p 2858 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	P-gP efflux biodistribution mucoadhesion resistance fluorescent micelles Chemistry QD1-999
spellingShingle	P-gP efflux biodistribution mucoadhesion resistance fluorescent micelles Chemistry QD1-999 Sobia Razzaq Aisha Rauf Abida Raza Sohail Akhtar Tanveer A. Tabish Mansur Abdullah Sandhu Muhammad Zaman Ibrahim M. Ibrahim Gul Shahnaz Abbas Rahdar Ana M. Díez-Pascual A Multifunctional Polymeric Micelle for Targeted Delivery of Paclitaxel by the Inhibition of the P-Glycoprotein Transporters
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	article
author	Sobia Razzaq Aisha Rauf Abida Raza Sohail Akhtar Tanveer A. Tabish Mansur Abdullah Sandhu Muhammad Zaman Ibrahim M. Ibrahim Gul Shahnaz Abbas Rahdar Ana M. Díez-Pascual
author_facet	Sobia Razzaq Aisha Rauf Abida Raza Sohail Akhtar Tanveer A. Tabish Mansur Abdullah Sandhu Muhammad Zaman Ibrahim M. Ibrahim Gul Shahnaz Abbas Rahdar Ana M. Díez-Pascual
author_sort	Sobia Razzaq
title	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_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_sort	multifunctional polymeric micelle for targeted delivery of paclitaxel by the inhibition of the p-glycoprotein transporters
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/5392668d811a4f03bcf1fa7882ced679
work_keys_str_mv	AT sobiarazzaq amultifunctionalpolymericmicellefortargeteddeliveryofpaclitaxelbytheinhibitionofthepglycoproteintransporters AT aisharauf amultifunctionalpolymericmicellefortargeteddeliveryofpaclitaxelbytheinhibitionofthepglycoproteintransporters AT abidaraza amultifunctionalpolymericmicellefortargeteddeliveryofpaclitaxelbytheinhibitionofthepglycoproteintransporters AT sohailakhtar amultifunctionalpolymericmicellefortargeteddeliveryofpaclitaxelbytheinhibitionofthepglycoproteintransporters AT tanveeratabish amultifunctionalpolymericmicellefortargeteddeliveryofpaclitaxelbytheinhibitionofthepglycoproteintransporters AT mansurabdullahsandhu amultifunctionalpolymericmicellefortargeteddeliveryofpaclitaxelbytheinhibitionofthepglycoproteintransporters AT muhammadzaman amultifunctionalpolymericmicellefortargeteddeliveryofpaclitaxelbytheinhibitionofthepglycoproteintransporters AT ibrahimmibrahim amultifunctionalpolymericmicellefortargeteddeliveryofpaclitaxelbytheinhibitionofthepglycoproteintransporters AT gulshahnaz amultifunctionalpolymericmicellefortargeteddeliveryofpaclitaxelbytheinhibitionofthepglycoproteintransporters AT abbasrahdar amultifunctionalpolymericmicellefortargeteddeliveryofpaclitaxelbytheinhibitionofthepglycoproteintransporters AT anamdiezpascual amultifunctionalpolymericmicellefortargeteddeliveryofpaclitaxelbytheinhibitionofthepglycoproteintransporters AT sobiarazzaq multifunctionalpolymericmicellefortargeteddeliveryofpaclitaxelbytheinhibitionofthepglycoproteintransporters AT aisharauf multifunctionalpolymericmicellefortargeteddeliveryofpaclitaxelbytheinhibitionofthepglycoproteintransporters AT abidaraza multifunctionalpolymericmicellefortargeteddeliveryofpaclitaxelbytheinhibitionofthepglycoproteintransporters AT sohailakhtar multifunctionalpolymericmicellefortargeteddeliveryofpaclitaxelbytheinhibitionofthepglycoproteintransporters AT tanveeratabish multifunctionalpolymericmicellefortargeteddeliveryofpaclitaxelbytheinhibitionofthepglycoproteintransporters AT mansurabdullahsandhu multifunctionalpolymericmicellefortargeteddeliveryofpaclitaxelbytheinhibitionofthepglycoproteintransporters AT muhammadzaman multifunctionalpolymericmicellefortargeteddeliveryofpaclitaxelbytheinhibitionofthepglycoproteintransporters AT ibrahimmibrahim multifunctionalpolymericmicellefortargeteddeliveryofpaclitaxelbytheinhibitionofthepglycoproteintransporters AT gulshahnaz multifunctionalpolymericmicellefortargeteddeliveryofpaclitaxelbytheinhibitionofthepglycoproteintransporters AT abbasrahdar multifunctionalpolymericmicellefortargeteddeliveryofpaclitaxelbytheinhibitionofthepglycoproteintransporters AT anamdiezpascual multifunctionalpolymericmicellefortargeteddeliveryofpaclitaxelbytheinhibitionofthepglycoproteintransporters
_version_	1718411074263318528

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

Ejemplares similares