Gram Scale Synthesis of Dual-Responsive Dendritic Polyglycerol Sulfate as Drug Delivery System
Biocompatible polymers with the ability to load and release a cargo at the site of action in a smart response to stimuli have attracted great attention in the field of drug delivery and cancer therapy. In this work, we synthesize a dual-responsive dendritic polyglycerol sulfate (DR-dPGS) drug delive...
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ftdatacite:10.17169/refubium-30225 2023-05-15T13:52:30+02:00 Gram Scale Synthesis of Dual-Responsive Dendritic Polyglycerol Sulfate as Drug Delivery System Reisbeck, Felix Ozimkovski, Alexander Cherri, Mariam Dimde, Mathias Quaas, Elisa Mohammadifar, Ehsan Achazi, Katharina Haag, Rainer 2021 https://dx.doi.org/10.17169/refubium-30225 https://refubium.fu-berlin.de/handle/fub188/30485 unknown Freie Universität Berlin https://doi.org/10.3390/polym13060982 https://dx.doi.org/10.3390/polym13060982 https://doi.org/10.3390/polym13060982 Creative Commons Attribution 4.0 International https://creativecommons.org/licenses/by/4.0/legalcode cc-by-4.0 CC-BY drug delivery system dual-responsiveness dendritic polyglycerol sulfates 500 Naturwissenschaften und Mathematik540 Chemie540 Chemie und zugeordnete Wissenschaften 600 Technik, Medizin, angewandte Wissenschaften610 Medizin und Gesundheit616 Krankheiten 600 Technik, Medizin, angewandte Wissenschaften610 Medizin und Gesundheit615 Pharmakologie, Therapeutik Text article-journal Wissenschaftlicher Artikel ScholarlyArticle 2021 ftdatacite https://doi.org/10.17169/refubium-30225 https://doi.org/10.3390/polym13060982 2021-11-05T12:55:41Z Biocompatible polymers with the ability to load and release a cargo at the site of action in a smart response to stimuli have attracted great attention in the field of drug delivery and cancer therapy. In this work, we synthesize a dual-responsive dendritic polyglycerol sulfate (DR-dPGS) drug delivery system by copolymerization of glycidol, ε-caprolactone and an epoxide monomer bearing a disulfide bond (SSG), followed by sulfation of terminal hydroxyl groups of the copolymer. The effect of different catalysts, including Lewis acids and organic bases, on the molecular weight, monomer content and polymer structure was investigated. The degradation of the polymer backbone was proven in presence of reducing agents and candida antarctica Lipase B (CALB) enzyme, which results in the cleavage of the disulfides and ester bonds, respectively. The hydrophobic anticancer drug Doxorubicin (DOX) was loaded in the polymer and the kinetic assessment showed an enhanced drug release with glutathione (GSH) or CALB as compared to controls and a synergistic effect of a combination of both stimuli. Cell uptake was studied by using confocal laser scanning microscopy with HeLa cells and showed the uptake of the Dox-loaded carriers and the release of the drug into the nucleus. Cytotoxicity tests with three different cancer cell lines showed good tolerability of the polymers of as high concentrations as 1 mg mL−1, while cancer cell growth was efficiently inhibited by DR-dPGS@Dox. Text Antarc* Antarctica DataCite Metadata Store (German National Library of Science and Technology) |
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drug delivery system dual-responsiveness dendritic polyglycerol sulfates 500 Naturwissenschaften und Mathematik540 Chemie540 Chemie und zugeordnete Wissenschaften 600 Technik, Medizin, angewandte Wissenschaften610 Medizin und Gesundheit616 Krankheiten 600 Technik, Medizin, angewandte Wissenschaften610 Medizin und Gesundheit615 Pharmakologie, Therapeutik |
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drug delivery system dual-responsiveness dendritic polyglycerol sulfates 500 Naturwissenschaften und Mathematik540 Chemie540 Chemie und zugeordnete Wissenschaften 600 Technik, Medizin, angewandte Wissenschaften610 Medizin und Gesundheit616 Krankheiten 600 Technik, Medizin, angewandte Wissenschaften610 Medizin und Gesundheit615 Pharmakologie, Therapeutik Reisbeck, Felix Ozimkovski, Alexander Cherri, Mariam Dimde, Mathias Quaas, Elisa Mohammadifar, Ehsan Achazi, Katharina Haag, Rainer Gram Scale Synthesis of Dual-Responsive Dendritic Polyglycerol Sulfate as Drug Delivery System |
topic_facet |
drug delivery system dual-responsiveness dendritic polyglycerol sulfates 500 Naturwissenschaften und Mathematik540 Chemie540 Chemie und zugeordnete Wissenschaften 600 Technik, Medizin, angewandte Wissenschaften610 Medizin und Gesundheit616 Krankheiten 600 Technik, Medizin, angewandte Wissenschaften610 Medizin und Gesundheit615 Pharmakologie, Therapeutik |
description |
Biocompatible polymers with the ability to load and release a cargo at the site of action in a smart response to stimuli have attracted great attention in the field of drug delivery and cancer therapy. In this work, we synthesize a dual-responsive dendritic polyglycerol sulfate (DR-dPGS) drug delivery system by copolymerization of glycidol, ε-caprolactone and an epoxide monomer bearing a disulfide bond (SSG), followed by sulfation of terminal hydroxyl groups of the copolymer. The effect of different catalysts, including Lewis acids and organic bases, on the molecular weight, monomer content and polymer structure was investigated. The degradation of the polymer backbone was proven in presence of reducing agents and candida antarctica Lipase B (CALB) enzyme, which results in the cleavage of the disulfides and ester bonds, respectively. The hydrophobic anticancer drug Doxorubicin (DOX) was loaded in the polymer and the kinetic assessment showed an enhanced drug release with glutathione (GSH) or CALB as compared to controls and a synergistic effect of a combination of both stimuli. Cell uptake was studied by using confocal laser scanning microscopy with HeLa cells and showed the uptake of the Dox-loaded carriers and the release of the drug into the nucleus. Cytotoxicity tests with three different cancer cell lines showed good tolerability of the polymers of as high concentrations as 1 mg mL−1, while cancer cell growth was efficiently inhibited by DR-dPGS@Dox. |
format |
Text |
author |
Reisbeck, Felix Ozimkovski, Alexander Cherri, Mariam Dimde, Mathias Quaas, Elisa Mohammadifar, Ehsan Achazi, Katharina Haag, Rainer |
author_facet |
Reisbeck, Felix Ozimkovski, Alexander Cherri, Mariam Dimde, Mathias Quaas, Elisa Mohammadifar, Ehsan Achazi, Katharina Haag, Rainer |
author_sort |
Reisbeck, Felix |
title |
Gram Scale Synthesis of Dual-Responsive Dendritic Polyglycerol Sulfate as Drug Delivery System |
title_short |
Gram Scale Synthesis of Dual-Responsive Dendritic Polyglycerol Sulfate as Drug Delivery System |
title_full |
Gram Scale Synthesis of Dual-Responsive Dendritic Polyglycerol Sulfate as Drug Delivery System |
title_fullStr |
Gram Scale Synthesis of Dual-Responsive Dendritic Polyglycerol Sulfate as Drug Delivery System |
title_full_unstemmed |
Gram Scale Synthesis of Dual-Responsive Dendritic Polyglycerol Sulfate as Drug Delivery System |
title_sort |
gram scale synthesis of dual-responsive dendritic polyglycerol sulfate as drug delivery system |
publisher |
Freie Universität Berlin |
publishDate |
2021 |
url |
https://dx.doi.org/10.17169/refubium-30225 https://refubium.fu-berlin.de/handle/fub188/30485 |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_relation |
https://doi.org/10.3390/polym13060982 https://dx.doi.org/10.3390/polym13060982 https://doi.org/10.3390/polym13060982 |
op_rights |
Creative Commons Attribution 4.0 International https://creativecommons.org/licenses/by/4.0/legalcode cc-by-4.0 |
op_rightsnorm |
CC-BY |
op_doi |
https://doi.org/10.17169/refubium-30225 https://doi.org/10.3390/polym13060982 |
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1766256785260281856 |