[en] Poly(ethylene glycol)-b-polyphosphoester (PEG-b-PPE) block copolymer nanoparticles are promising carriers for poorly water soluble drugs. To enhance the drug loading capacity and efficiency of such micelles, a strategy was investigated for increasing the lipophilicity of the PPE block of these PEG-b-PPE amphiphilic copolymers. A PEG-b-PPE copolymer bearing pendant vinyl groups along the PPE block was synthesized and then modified by thiol-ene click reaction with thiols bearing either a long linear alkyl chain (dodecyl) or a tocopherol moiety. Ketoconazole was used as model for hydrophobic drugs. Comparison of the drug loading with PEG-b-PPE bearing shorter pendant groups is reported evidencing the key role of the structure of the pendant group on the PPE backbone. Finally, a first evidence of the biocompatibility of these novel PEG-b-PPE copolymers was achieved by performing cytotoxicity tests. The PEG-b-PPE derived by tocopherol was evidenced as particularly promising as delivery system of poorly water-soluble drugs.
Research Center/Unit :
Complex and Entangled Systems from Atoms to Materials (CESAM) Research Unit Center for Education and Research on Macromolecules (CERM)
Disciplines :
Chemistry Materials science & engineering
Author, co-author :
Vanslambrouck, Stéphanie ; University of Liège (ULiège), Complex and Entangled Systems from Atoms to Materials (CESAM) Research Unit, Center for Education and Research on Macromolecules (CERM), Belgium
Riva, Raphaël ; University of Liège (ULiège), Complex and Entangled Systems from Atoms to Materials (CESAM) Research Unit, Center for Education and Research on Macromolecules (CERM), Belgium
Ucakar, Bernard; Université catholique de Louvain (UCL), Brussels, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Belgium
Préat, Véronique; Université catholique de Louvain (UCL), Brussels, Louvain Drug Research Institute, Advanced Drug Delivery and Biomaterials, Belgium
Gagliardi, Mick; University of Maastricht, Faculty of Health, Medicine and Life Science, Department of Physiology, the Netherlands
Daniel, Daniel G. M.; University of Maastricht, Faculty of Health, Medicine and Life Science, Department of Physiology, the Netherlands
Lecomte, Philippe ; University of Liège (ULiège), Complex and Entangled Systems from Atoms to Materials (CESAM) Research Unit, Center for Education and Research on Macromolecules (CERM), Belgium
Jérôme, Christine ; University of Liège (ULiège), Complex and Entangled Systems from Atoms to Materials (CESAM) Research Unit, Center for Education and Research on Macromolecules (CERM), Belgium
Language :
English
Title :
Thiol-ene reaction: an efficient tool to design lipophilic polyphosphoesters for drug delivery systems
Publication date :
20 March 2021
Journal title :
Molecules
eISSN :
1420-3049
Publisher :
Multidisciplinary Digital Publishing Institute (MDPI), Switzerland
scite shows how a scientific paper has been cited by providing the context of the citation, a classification describing whether it supports, mentions, or contrasts the cited claim, and a label indicating in which section the citation was made.
Bibliography
Lapienis, G.; Penczek, S. Kinetics and thermodynamics of the polymerization of the cyclic phosphate esters. II. Cationic polymerization of 2-methoxy-2-oxo-1,3,2-dioxaphosphorinane (1,3-propylene methyl phosphate). Macromolecules 1974, 7, 166–174. [CrossRef]
Dove, A.P. Organic catalysis for ring-opening polymerization. ACS Macro Lett. 2012, 1, 1409–1412. [CrossRef]
Clément, B.; Grignard, B.; Koole, L.; Jérome, C.; Lecomte, P. Metal-free strategies for the synthesis of functional and well-defined polyphosphoesters. Macromolecules 2012, 45, 4476–4486. [CrossRef]
Riva, R.; Shah, U.; Thomassin, J.M.; Yilmaz, Z.; Lecat, A.; Colige, A.; Jérôme, C. Design of degradable polyphosphoester networks with tailor-made stiffness and hydrophilicity as scaffolds for tissue engineering. Biomacromolecules 2020, 21, 349–355. [CrossRef] [PubMed]
Wang, Y.-C.; Yuan, Y.-Y.; Du, J.-Z.; Yang, X.-Z.; Wang, J. Recent progress in polyphosphoesters: From controlled synthesis to biomedical applications. Macromol. Biosci. 2009, 9, 1154–1164. [CrossRef] [PubMed]
Becker, G.; Wurm, F.R. Functional biodegradable polymers via ring-opening polymerization of monomers without protective groups. Chem. Soc. Rev. 2018, 47, 7739–7782. [CrossRef] [PubMed]
Ergül Yilmaz, Z.; Jérôme, C. Polyphosphoesters: New trends in synthesis and drug delivery applications. Macromol. Biosci. 2016, 16, 1745–1751. [CrossRef]
Pelosi, C.; Tinè, M.R.; Wurm, F.R. Main-chain water-soluble polyphosphoesters: Multi-functional polymers as degradable PEG-alternatives for biomedical applications. Eur. Polym. J. 2020, 141, 110079. [CrossRef]
Wang, Y.-C.; Yuan, Y.-Y.; Wang, F.; Wang, J. Syntheses and characterization of block copolymers of poly(aliphatic ester) with clickable polyphosphoester. J. Polym. Sci. Part A 2011, 49, 487–494. [CrossRef]
Zhang, S.; Li, A.; Zou, J.; Lin, L.Y.; Wooley, K.L. Facile synthesis of clickable, water-soluble, and degradable polyphosphoesters. ACS Macro Lett. 2012, 1, 328–333. [CrossRef] [PubMed]
Zhang, S.; Zou, J.; Elsabahy, M.; Karwa, A.; Li, A.; Moore, D.A.; Dorshowdf, R.B.; Wooley, K.L. Poly(ethylene oxide)-block-polyphosphester-based paclitaxel conjugates as a platform for ultra-high paclitaxel-loaded multifunctional nanoparticles. Chem. Sci. 2013, 4, 2122–2126. [CrossRef] [PubMed]
Du, J.-Z.; Du, X.J.; Mao, C.-Q.; Wang, J. Tailor-made dual pH-sensitive polymer-doxorubicin nanoparticles for efficient anticancer drug delivery. J. Am. Chem. Soc. 2011, 133, 17560–17563. [CrossRef]
Yang, X.-Z.; Du, J.Z.; Dou, S.; Mao, C.-Q.; Long, H.Y.; Wang, J. Sheddable ternary nanoparticles for tumor acidity-targeted siRNA delivery. ACS Nano 2012, 6, 771–781. [CrossRef] [PubMed]
Yuan, Y.-Y.; Mao, C.-Q.; Du, X.-J.; Du, J.-Z.; Wang, F.; Wang, J. Surface charge switchable nanoparticles based on zwitterionic polymer for enhanced drug delivery to tumor. Adv. Mater. 2012, 24, 5476–5480. [CrossRef]
Yuan, Y.-Y.; Du, J.-Z.; Wang, J. Two consecutive click reactions as a general route to functional cyclic polyesters. Chem. Commun. 2012, 48, 570–572. [CrossRef] [PubMed]
Sun, C.-Y.; Dou, S.; Du, J.-Z.; Yang, X.-Z.; Li, Y.-P.; Wang, J. Doxorubicin conjugate of poly(ethylene glycol)-block-polyphosphoester for cancer therapy. Adv. Healthc. Mater. 2014, 3, 261–272. [CrossRef]
Baeten, E.; Vanslambrouck, S.; Jérôme, C.; Lecomte, P.; Junkers, T. Anionic flow polymerizations toward functional polyphospho-esters in microreactors: Polymerization and UV-modification. Eur. Polym. J. 2016, 80, 208–218. [CrossRef]
Zhang, S.; Zou, J.; Zhang, F.; Elsabahy, M.; Felder, S.E.; Zhu, J.; Pochan, D.J.; Wooley, K.L. Rapid and versatile construction of diverse and functional nanostructures derived from a polyphosphoester-based biomimetic block copolymer system. J. Am. Chem. Soc. 2012, 134, 18467–18474. [CrossRef] [PubMed]
Lim, Y.H.; Heo, G.S.; Cho, S.; Wooley, K.L. Construction of a reactive diblock copolymer, polyphosphoester block-poly(L-lactide), as a versatile framework for functional materials that are capable of full degradation and nanoscopic assembly formation. ACS Macro Lett. 2013, 2, 785–789. [CrossRef] [PubMed]
Ergül Yilmaz, Z.; Debuigne, A.; Calvignac, B.; Boury, F.; Jérôme, C. Double hydrophilic polyphosphoester containing copolymers as efficient templating agents for calcium carbonate microparticles. J. Mater. Chem. B 2015, 3, 7227–7236. [CrossRef]
Sun, C.-Y.; Ma, Y.-C.; Cao, Z.-Y.; Li, D.-D.; Fan, F.; Wang, J.-X.; Tao, W.; Yang, X.-Z. Effect of hydrophobicity of core on the anticancer efficiency of micelles as drug delivery carriers. ACS Appl. Mater. Interfaces 2014, 6, 22709–22718. [CrossRef] [PubMed]
Vanslambrouck, S.; Clément, B.; Riva, R.; Koole, L.H.; Molin, D.G.M.; Broze, G.; Lecomte, P.; Jérôme, C. Synthesis and tensioactive properties of PEO-b-polyphosphate copolymers. RSC Adv. 2015, 5, 27330–27337. [CrossRef]
Karmowski, J.; Hintze, V.; Kschonsek, J.; Killenberg, M.; Böhm, V. Antioxidant activities of tocopherols/tocotrienols and lipophilic antioxidant capacity of wheat, vegetable oils, milk and milk cream by using photochemiluminescence. Food Chem. 2015, 175, 593–600. [CrossRef]
Constantinides, P.P.; Han, J.; Davis, S.S. Advances in the use of tocols as drug delivery vehicles. Pharm. Res. 2006, 23, 243–255. [CrossRef] [PubMed]
Duhem, N.; Danhier, F.; Préat, V. Vitamin E-based nanomedicines for anti-cancer drug delivery. J. Control. Release 2014, 182, 33–44. [CrossRef] [PubMed]
Brigelius-Flohé, R.; Traber, M.G. Vitamin E: Function and metabolism. FASEB J. 1999, 13, 1145–1155. [CrossRef]
Lim, Y.H.; Heo, G.S.; Rezenom, Y.H.; Pollack, S.; Raymond, J.E.; Elsabahy, M.; Wooley, K.L. Development of a vinyl ether-functionalized polyphosphoester as a template for multiple postpolymerization conjugation chemistries and study of core degradable polymeric nanoparticles. Macromolecules 2014, 47, 4634–4644. [CrossRef] [PubMed]
Balata, G.; Maahdi, M.; Bakera, R.A. Improvement of solubility and dissolution properties of ketoconazole by solid dispersions and inclusion complexes. Asian J. Pharm. Sci. 2010, 5, 1–12.
Gaucher, G.; Dufresne, M.-H.; Sant, V.P.; Kang, N.; Maysinger, D.; Leroux, J.-C. Block copolymer micelles: Preparation, characterization and application in drug delivery. J. Control. Release 2005, 109, 169–188. [CrossRef]
Ergül Yilmaz, Z.; Vanslambrouck, S.; Cajot, S.; Thiry, J.; Debuigne, A.; Lecomte, P.; Jérôme, C.; Riva, R. Core cross-linked micelles of polyphosphoester containing amphiphilic block copolymers as drug nanocarriers. RSC Adv. 2016, 6, 42081–42088. [CrossRef]
Similar publications
Sorry the service is unavailable at the moment. Please try again later.
This website uses cookies to improve user experience. Read more
Save & Close
Accept all
Decline all
Show detailsHide details
Cookie declaration
About cookies
Strictly necessary
Performance
Strictly necessary cookies allow core website functionality such as user login and account management. The website cannot be used properly without strictly necessary cookies.
This cookie is used by Cookie-Script.com service to remember visitor cookie consent preferences. It is necessary for Cookie-Script.com cookie banner to work properly.
Performance cookies are used to see how visitors use the website, eg. analytics cookies. Those cookies cannot be used to directly identify a certain visitor.
Used to store the attribution information, the referrer initially used to visit the website
Cookies are small text files that are placed on your computer by websites that you visit. Websites use cookies to help users navigate efficiently and perform certain functions. Cookies that are required for the website to operate properly are allowed to be set without your permission. All other cookies need to be approved before they can be set in the browser.
You can change your consent to cookie usage at any time on our Privacy Policy page.