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A unique amphiphilic triblock copolymer, nontoxic to human blood and potential supramolecular drug delivery system for dexamethasone

The drug delivery system (DDS) often causes toxicity, triggering undesired cellular injuries. Thus, developing supramolecules used as DDS with tunable self-assembly and nontoxic behavior is highly desired. To address this, we aimed to develop a tunable amphiphilic ABA-type triblock copolymer that is...

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Autores principales: Mushtaq, Irrum, Akhter, Zareen, Farooq, Muhammad, Jabeen, Farukh, Rehman, Ashfaq Ur, Rehman, Sadia, Ayub, Sidra, Mirza, Bushra, Siddiq, Muhammad, Zaman, Farasat
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8563740/
https://www.ncbi.nlm.nih.gov/pubmed/34728694
http://dx.doi.org/10.1038/s41598-021-00871-w
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author Mushtaq, Irrum
Akhter, Zareen
Farooq, Muhammad
Jabeen, Farukh
Rehman, Ashfaq Ur
Rehman, Sadia
Ayub, Sidra
Mirza, Bushra
Siddiq, Muhammad
Zaman, Farasat
author_facet Mushtaq, Irrum
Akhter, Zareen
Farooq, Muhammad
Jabeen, Farukh
Rehman, Ashfaq Ur
Rehman, Sadia
Ayub, Sidra
Mirza, Bushra
Siddiq, Muhammad
Zaman, Farasat
author_sort Mushtaq, Irrum
collection PubMed
description The drug delivery system (DDS) often causes toxicity, triggering undesired cellular injuries. Thus, developing supramolecules used as DDS with tunable self-assembly and nontoxic behavior is highly desired. To address this, we aimed to develop a tunable amphiphilic ABA-type triblock copolymer that is nontoxic to human blood cells but also capable of self-assembling, binding and releasing the clinically used drug dexamethasone. We synthesized an ABA-type amphiphilic triblock copolymer (P2L) by incorporating tetra(aniline) TANI as a hydrophobic and redox active segment along with monomethoxy end-capped polyethylene glycol (mPEG(2k); M(w) = 2000 g mol(−1)) as biocompatible, flexible and hydrophilic part. Cell cytotoxicity was measured in whole human blood in vitro and lung cancer cells. Polymer-drug interactions were investigated by UV–Vis spectroscopy and computational analysis. Our synthesized copolymer P2L exhibited tuned self-assembly behavior with and without external stimuli and showed no toxicity in human blood samples. Computational analysis showed that P2L can encapsulate the clinically used drug dexamethasone and that drug uptake or release can also be triggered under oxidation or low pH conditions. In conclusion, copolymer P2L is nontoxic to human blood cells with the potential to carry and release anticancer/anti-inflammatory drug dexamethasone. These findings may open up further investigations into implantable drug delivery systems/devices with precise drug administration and controlled release at specific locations.
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spelling pubmed-85637402021-11-03 A unique amphiphilic triblock copolymer, nontoxic to human blood and potential supramolecular drug delivery system for dexamethasone Mushtaq, Irrum Akhter, Zareen Farooq, Muhammad Jabeen, Farukh Rehman, Ashfaq Ur Rehman, Sadia Ayub, Sidra Mirza, Bushra Siddiq, Muhammad Zaman, Farasat Sci Rep Article The drug delivery system (DDS) often causes toxicity, triggering undesired cellular injuries. Thus, developing supramolecules used as DDS with tunable self-assembly and nontoxic behavior is highly desired. To address this, we aimed to develop a tunable amphiphilic ABA-type triblock copolymer that is nontoxic to human blood cells but also capable of self-assembling, binding and releasing the clinically used drug dexamethasone. We synthesized an ABA-type amphiphilic triblock copolymer (P2L) by incorporating tetra(aniline) TANI as a hydrophobic and redox active segment along with monomethoxy end-capped polyethylene glycol (mPEG(2k); M(w) = 2000 g mol(−1)) as biocompatible, flexible and hydrophilic part. Cell cytotoxicity was measured in whole human blood in vitro and lung cancer cells. Polymer-drug interactions were investigated by UV–Vis spectroscopy and computational analysis. Our synthesized copolymer P2L exhibited tuned self-assembly behavior with and without external stimuli and showed no toxicity in human blood samples. Computational analysis showed that P2L can encapsulate the clinically used drug dexamethasone and that drug uptake or release can also be triggered under oxidation or low pH conditions. In conclusion, copolymer P2L is nontoxic to human blood cells with the potential to carry and release anticancer/anti-inflammatory drug dexamethasone. These findings may open up further investigations into implantable drug delivery systems/devices with precise drug administration and controlled release at specific locations. Nature Publishing Group UK 2021-11-02 /pmc/articles/PMC8563740/ /pubmed/34728694 http://dx.doi.org/10.1038/s41598-021-00871-w Text en © The Author(s) 2021 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 Article
Mushtaq, Irrum
Akhter, Zareen
Farooq, Muhammad
Jabeen, Farukh
Rehman, Ashfaq Ur
Rehman, Sadia
Ayub, Sidra
Mirza, Bushra
Siddiq, Muhammad
Zaman, Farasat
A unique amphiphilic triblock copolymer, nontoxic to human blood and potential supramolecular drug delivery system for dexamethasone
title A unique amphiphilic triblock copolymer, nontoxic to human blood and potential supramolecular drug delivery system for dexamethasone
title_full A unique amphiphilic triblock copolymer, nontoxic to human blood and potential supramolecular drug delivery system for dexamethasone
title_fullStr A unique amphiphilic triblock copolymer, nontoxic to human blood and potential supramolecular drug delivery system for dexamethasone
title_full_unstemmed A unique amphiphilic triblock copolymer, nontoxic to human blood and potential supramolecular drug delivery system for dexamethasone
title_short A unique amphiphilic triblock copolymer, nontoxic to human blood and potential supramolecular drug delivery system for dexamethasone
title_sort unique amphiphilic triblock copolymer, nontoxic to human blood and potential supramolecular drug delivery system for dexamethasone
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8563740/
https://www.ncbi.nlm.nih.gov/pubmed/34728694
http://dx.doi.org/10.1038/s41598-021-00871-w
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