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Well-Defined Shell-Sheddable Core-Crosslinked Micelles with pH and Oxidation Dual-Response for On-Demand Drug Delivery

Micellar-nanocarrier-based drug delivery systems possessing characteristics such as an excellent circulation stability, inhibited premature release and on-demand site-specific release are urgently needed for enhanced therapeutic efficacy. Therefore, a novel kind of shell-sheddable core-crosslinked p...

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Autores principales: Cheng, Xinfeng, Li, Qiyang, Sun, Xiaomeng, Ma, Yuxin, Xie, Huanping, Kong, Weiguang, Du, Xianchao, Zhang, Zhenghui, Qiu, Dongfang, Jin, Yong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10180867/
https://www.ncbi.nlm.nih.gov/pubmed/37177138
http://dx.doi.org/10.3390/polym15091990
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author Cheng, Xinfeng
Li, Qiyang
Sun, Xiaomeng
Ma, Yuxin
Xie, Huanping
Kong, Weiguang
Du, Xianchao
Zhang, Zhenghui
Qiu, Dongfang
Jin, Yong
author_facet Cheng, Xinfeng
Li, Qiyang
Sun, Xiaomeng
Ma, Yuxin
Xie, Huanping
Kong, Weiguang
Du, Xianchao
Zhang, Zhenghui
Qiu, Dongfang
Jin, Yong
author_sort Cheng, Xinfeng
collection PubMed
description Micellar-nanocarrier-based drug delivery systems possessing characteristics such as an excellent circulation stability, inhibited premature release and on-demand site-specific release are urgently needed for enhanced therapeutic efficacy. Therefore, a novel kind of shell-sheddable core-crosslinked polymeric micelles with pH and oxidation dual-triggered on-demand drug release behavior was facilely constructed. The multifunctional micelles were self-assembled from a carefully designed amphiphilic triblock PEGylated polyurethane (PEG-acetal-PUBr-acetal-PEG) employing an acid-labile acetal linker at the hydrophilic–hydrophobic interface and pendant reactive bromo-containing polyurethane (PU) as the hydrophobic block, followed by a post-crosslinking via oxidation-cleavable diselenide linkages. These well-defined micelles exhibited an enhanced structural stability against dilution, achieved through the incorporation of diselenide crosslinkers. As expected, they were found to possess dual pH- and oxidation-responsive dissociation behaviors when exposure to acid pH (~5.0) and 50 mM H(2)O(2) conditions, as evidenced using dynamic light-scattering (DLS) and atomic force microscopy (AFM) analyses. An in vitro drug release investigation showed that the drug indomethacin (IND) could be efficiently encapsulated in the micelles, which demonstrated an inhibited premature release compared to the non-crosslinked ones. It is noteworthy that the resulting micelles could efficiently release entrapped drugs at a fast rate in response to either pH or oxidation stimuli. Moreover, the release could be significantly accelerated in the presence of both acid pH and oxidation conditions, relative to a single stimulus, owing to the synergetic degradation of micelles through pH-induced dePEGylation and oxidation-triggered decrosslinking processes. The proposed shell-sheddable core-crosslinked micelles with a pH and oxidation dual-response could be potential candidates as drug carriers for on-demand drug delivery.
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spelling pubmed-101808672023-05-13 Well-Defined Shell-Sheddable Core-Crosslinked Micelles with pH and Oxidation Dual-Response for On-Demand Drug Delivery Cheng, Xinfeng Li, Qiyang Sun, Xiaomeng Ma, Yuxin Xie, Huanping Kong, Weiguang Du, Xianchao Zhang, Zhenghui Qiu, Dongfang Jin, Yong Polymers (Basel) Article Micellar-nanocarrier-based drug delivery systems possessing characteristics such as an excellent circulation stability, inhibited premature release and on-demand site-specific release are urgently needed for enhanced therapeutic efficacy. Therefore, a novel kind of shell-sheddable core-crosslinked polymeric micelles with pH and oxidation dual-triggered on-demand drug release behavior was facilely constructed. The multifunctional micelles were self-assembled from a carefully designed amphiphilic triblock PEGylated polyurethane (PEG-acetal-PUBr-acetal-PEG) employing an acid-labile acetal linker at the hydrophilic–hydrophobic interface and pendant reactive bromo-containing polyurethane (PU) as the hydrophobic block, followed by a post-crosslinking via oxidation-cleavable diselenide linkages. These well-defined micelles exhibited an enhanced structural stability against dilution, achieved through the incorporation of diselenide crosslinkers. As expected, they were found to possess dual pH- and oxidation-responsive dissociation behaviors when exposure to acid pH (~5.0) and 50 mM H(2)O(2) conditions, as evidenced using dynamic light-scattering (DLS) and atomic force microscopy (AFM) analyses. An in vitro drug release investigation showed that the drug indomethacin (IND) could be efficiently encapsulated in the micelles, which demonstrated an inhibited premature release compared to the non-crosslinked ones. It is noteworthy that the resulting micelles could efficiently release entrapped drugs at a fast rate in response to either pH or oxidation stimuli. Moreover, the release could be significantly accelerated in the presence of both acid pH and oxidation conditions, relative to a single stimulus, owing to the synergetic degradation of micelles through pH-induced dePEGylation and oxidation-triggered decrosslinking processes. The proposed shell-sheddable core-crosslinked micelles with a pH and oxidation dual-response could be potential candidates as drug carriers for on-demand drug delivery. MDPI 2023-04-23 /pmc/articles/PMC10180867/ /pubmed/37177138 http://dx.doi.org/10.3390/polym15091990 Text en © 2023 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
Cheng, Xinfeng
Li, Qiyang
Sun, Xiaomeng
Ma, Yuxin
Xie, Huanping
Kong, Weiguang
Du, Xianchao
Zhang, Zhenghui
Qiu, Dongfang
Jin, Yong
Well-Defined Shell-Sheddable Core-Crosslinked Micelles with pH and Oxidation Dual-Response for On-Demand Drug Delivery
title Well-Defined Shell-Sheddable Core-Crosslinked Micelles with pH and Oxidation Dual-Response for On-Demand Drug Delivery
title_full Well-Defined Shell-Sheddable Core-Crosslinked Micelles with pH and Oxidation Dual-Response for On-Demand Drug Delivery
title_fullStr Well-Defined Shell-Sheddable Core-Crosslinked Micelles with pH and Oxidation Dual-Response for On-Demand Drug Delivery
title_full_unstemmed Well-Defined Shell-Sheddable Core-Crosslinked Micelles with pH and Oxidation Dual-Response for On-Demand Drug Delivery
title_short Well-Defined Shell-Sheddable Core-Crosslinked Micelles with pH and Oxidation Dual-Response for On-Demand Drug Delivery
title_sort well-defined shell-sheddable core-crosslinked micelles with ph and oxidation dual-response for on-demand drug delivery
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10180867/
https://www.ncbi.nlm.nih.gov/pubmed/37177138
http://dx.doi.org/10.3390/polym15091990
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