Stimuli-Responsive Triblock Terpolymer Conversion into Multi-Stimuli-Responsive Micelles with Dynamic Covalent Bonds for Drug Delivery through a Quick and Controllable Post-Polymerization Reaction
Stimuli-responsive copolymers are of great interest for targeted drug delivery. This study reports on a controllable post-polymerization quaternization with 2-bromomethyl-4-fluorophenylboronic acid of the poly(4-vinyl pyridine) (P4VP) block of a common poly(styrene)-<i>b</i>-poly(4-vinyl...
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| Format: | Article |
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MDPI AG
2023-01-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/1/288 |
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| author | Eva Hlavatovičová Roberto Fernandez-Alvarez Katarzyna Byś Sami Kereïche Tarun K. Mandal Leonard Ionut Atanase Miroslav Štěpánek Mariusz Uchman |
| author_facet | Eva Hlavatovičová Roberto Fernandez-Alvarez Katarzyna Byś Sami Kereïche Tarun K. Mandal Leonard Ionut Atanase Miroslav Štěpánek Mariusz Uchman |
| author_sort | Eva Hlavatovičová |
| collection | DOAJ |
| description | Stimuli-responsive copolymers are of great interest for targeted drug delivery. This study reports on a controllable post-polymerization quaternization with 2-bromomethyl-4-fluorophenylboronic acid of the poly(4-vinyl pyridine) (P4VP) block of a common poly(styrene)-<i>b</i>-poly(4-vinyl pyridine)-<i>b</i>-poly(ethylene oxide) (SVE) triblock terpolymer in order to achieve a selective responsivity to various diols. For this purpose, a reproducible method was established for P4VP block quaternization at a defined ratio, confirming the reaction yield by <sup>11</sup>B, <sup>1</sup>H NMR. Then, a reproducible self-assembly protocol is designed for preparing stable micelles from functionalized stimuli-responsive triblock terpolymers, which are characterized by light scattering and by cryogenic transmission electron microscopy. In addition, UV-Vis spectroscopy is used to monitor the boron-ester bonding and hydrolysis with alizarin as a model drug and to study encapsulation and release of this drug, induced by sensing with three geminal diols: fructose, galactose and ascorbic acid. The obtained results show that only the latter, with the vicinal diol group on sp<sup>2</sup>-hybridized carbons, was efficient for alizarin release. Therefore, the post-polymerization method for triblock terpolymer functionalization presented in this study allows for preparation of specific stimuli-responsive systems with a high potential for targeted drug delivery, especially for cancer treatment. |
| first_indexed | 2024-03-09T11:26:59Z |
| format | Article |
| id | doaj.art-ddac3ba756184deba7fea6adada52fef |
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| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T11:26:59Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-ddac3ba756184deba7fea6adada52fef2023-12-01T00:00:23ZengMDPI AGPharmaceutics1999-49232023-01-0115128810.3390/pharmaceutics15010288Stimuli-Responsive Triblock Terpolymer Conversion into Multi-Stimuli-Responsive Micelles with Dynamic Covalent Bonds for Drug Delivery through a Quick and Controllable Post-Polymerization ReactionEva Hlavatovičová0Roberto Fernandez-Alvarez1Katarzyna Byś2Sami Kereïche3Tarun K. Mandal4Leonard Ionut Atanase5Miroslav Štěpánek6Mariusz Uchman7Department of Physical and Macromolecular Chemistry, Charles University, Hlavova 2030, 12843 Prague 2, Czech RepublicDepartment of Physical and Macromolecular Chemistry, Charles University, Hlavova 2030, 12843 Prague 2, Czech RepublicDepartment of Physical and Macromolecular Chemistry, Charles University, Hlavova 2030, 12843 Prague 2, Czech RepublicDepartment of Physical and Macromolecular Chemistry, Charles University, Hlavova 2030, 12843 Prague 2, Czech RepublicSchool of Chemical Sciences, Indian Association for the Cultivation of Science, Jadavpur, Kolkata 700032, IndiaFaculty of Medical Dentistry, “Apollonia” University of Iasi, 700511 Iasi, RomaniaDepartment of Physical and Macromolecular Chemistry, Charles University, Hlavova 2030, 12843 Prague 2, Czech RepublicDepartment of Physical and Macromolecular Chemistry, Charles University, Hlavova 2030, 12843 Prague 2, Czech RepublicStimuli-responsive copolymers are of great interest for targeted drug delivery. This study reports on a controllable post-polymerization quaternization with 2-bromomethyl-4-fluorophenylboronic acid of the poly(4-vinyl pyridine) (P4VP) block of a common poly(styrene)-<i>b</i>-poly(4-vinyl pyridine)-<i>b</i>-poly(ethylene oxide) (SVE) triblock terpolymer in order to achieve a selective responsivity to various diols. For this purpose, a reproducible method was established for P4VP block quaternization at a defined ratio, confirming the reaction yield by <sup>11</sup>B, <sup>1</sup>H NMR. Then, a reproducible self-assembly protocol is designed for preparing stable micelles from functionalized stimuli-responsive triblock terpolymers, which are characterized by light scattering and by cryogenic transmission electron microscopy. In addition, UV-Vis spectroscopy is used to monitor the boron-ester bonding and hydrolysis with alizarin as a model drug and to study encapsulation and release of this drug, induced by sensing with three geminal diols: fructose, galactose and ascorbic acid. The obtained results show that only the latter, with the vicinal diol group on sp<sup>2</sup>-hybridized carbons, was efficient for alizarin release. Therefore, the post-polymerization method for triblock terpolymer functionalization presented in this study allows for preparation of specific stimuli-responsive systems with a high potential for targeted drug delivery, especially for cancer treatment.https://www.mdpi.com/1999-4923/15/1/288poly(4-vinyl pyridine)quaternizationpoly(styrene)-<i>b</i>-poly(4-vinyl pyridine)-<i>b</i>-poly(ethylene oxide) terpolymermicellesalizarindrug delivery systems |
| spellingShingle | Eva Hlavatovičová Roberto Fernandez-Alvarez Katarzyna Byś Sami Kereïche Tarun K. Mandal Leonard Ionut Atanase Miroslav Štěpánek Mariusz Uchman Stimuli-Responsive Triblock Terpolymer Conversion into Multi-Stimuli-Responsive Micelles with Dynamic Covalent Bonds for Drug Delivery through a Quick and Controllable Post-Polymerization Reaction Pharmaceutics poly(4-vinyl pyridine) quaternization poly(styrene)-<i>b</i>-poly(4-vinyl pyridine)-<i>b</i>-poly(ethylene oxide) terpolymer micelles alizarin drug delivery systems |
| title | Stimuli-Responsive Triblock Terpolymer Conversion into Multi-Stimuli-Responsive Micelles with Dynamic Covalent Bonds for Drug Delivery through a Quick and Controllable Post-Polymerization Reaction |
| title_full | Stimuli-Responsive Triblock Terpolymer Conversion into Multi-Stimuli-Responsive Micelles with Dynamic Covalent Bonds for Drug Delivery through a Quick and Controllable Post-Polymerization Reaction |
| title_fullStr | Stimuli-Responsive Triblock Terpolymer Conversion into Multi-Stimuli-Responsive Micelles with Dynamic Covalent Bonds for Drug Delivery through a Quick and Controllable Post-Polymerization Reaction |
| title_full_unstemmed | Stimuli-Responsive Triblock Terpolymer Conversion into Multi-Stimuli-Responsive Micelles with Dynamic Covalent Bonds for Drug Delivery through a Quick and Controllable Post-Polymerization Reaction |
| title_short | Stimuli-Responsive Triblock Terpolymer Conversion into Multi-Stimuli-Responsive Micelles with Dynamic Covalent Bonds for Drug Delivery through a Quick and Controllable Post-Polymerization Reaction |
| title_sort | stimuli responsive triblock terpolymer conversion into multi stimuli responsive micelles with dynamic covalent bonds for drug delivery through a quick and controllable post polymerization reaction |
| topic | poly(4-vinyl pyridine) quaternization poly(styrene)-<i>b</i>-poly(4-vinyl pyridine)-<i>b</i>-poly(ethylene oxide) terpolymer micelles alizarin drug delivery systems |
| url | https://www.mdpi.com/1999-4923/15/1/288 |
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