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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2021
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ftdoajarticles:oai:doaj.org/article:e5fa0db08d2b460382221c719e826253 2023-05-15T14:03:34+02:00 Gram Scale Synthesis of Dual-Responsive Dendritic Polyglycerol Sulfate as Drug Delivery System Felix Reisbeck Alexander Ozimkovski Mariam Cherri Mathias Dimde Elisa Quaas Ehsan Mohammadifar Katharina Achazi Rainer Haag 2021-03-01T00:00:00Z https://doi.org/10.3390/polym13060982 https://doaj.org/article/e5fa0db08d2b460382221c719e826253 EN eng MDPI AG https://www.mdpi.com/2073-4360/13/6/982 https://doaj.org/toc/2073-4360 doi:10.3390/polym13060982 2073-4360 https://doaj.org/article/e5fa0db08d2b460382221c719e826253 Polymers, Vol 13, Iss 982, p 982 (2021) drug delivery system dual-responsiveness dendritic polyglycerol sulfates Organic chemistry QD241-441 article 2021 ftdoajarticles https://doi.org/10.3390/polym13060982 2022-12-31T07:44:43Z 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. Article in Journal/Newspaper Antarc* Antarctica Directory of Open Access Journals: DOAJ Articles Polymers 13 6 982 |
institution |
Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
drug delivery system dual-responsiveness dendritic polyglycerol sulfates Organic chemistry QD241-441 |
spellingShingle |
drug delivery system dual-responsiveness dendritic polyglycerol sulfates Organic chemistry QD241-441 Felix Reisbeck Alexander Ozimkovski Mariam Cherri Mathias Dimde Elisa Quaas Ehsan Mohammadifar Katharina Achazi Rainer Haag Gram Scale Synthesis of Dual-Responsive Dendritic Polyglycerol Sulfate as Drug Delivery System |
topic_facet |
drug delivery system dual-responsiveness dendritic polyglycerol sulfates Organic chemistry QD241-441 |
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 |
Article in Journal/Newspaper |
author |
Felix Reisbeck Alexander Ozimkovski Mariam Cherri Mathias Dimde Elisa Quaas Ehsan Mohammadifar Katharina Achazi Rainer Haag |
author_facet |
Felix Reisbeck Alexander Ozimkovski Mariam Cherri Mathias Dimde Elisa Quaas Ehsan Mohammadifar Katharina Achazi Rainer Haag |
author_sort |
Felix Reisbeck |
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 |
MDPI AG |
publishDate |
2021 |
url |
https://doi.org/10.3390/polym13060982 https://doaj.org/article/e5fa0db08d2b460382221c719e826253 |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_source |
Polymers, Vol 13, Iss 982, p 982 (2021) |
op_relation |
https://www.mdpi.com/2073-4360/13/6/982 https://doaj.org/toc/2073-4360 doi:10.3390/polym13060982 2073-4360 https://doaj.org/article/e5fa0db08d2b460382221c719e826253 |
op_doi |
https://doi.org/10.3390/polym13060982 |
container_title |
Polymers |
container_volume |
13 |
container_issue |
6 |
container_start_page |
982 |
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1766274267015544832 |