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Polymer Chemistry 2018 Polymer Sciences
ISSN: 2471-9935 Page 34
March 26-28, 2018
Vienna, Austria
3rd Edition of International Conference and Exhibition on
Polymer Chemistry
Native chemical ligation (NCL) is an attractive method to
covalently cross-link polymers, because of its ability to
react under physiological conditions avoiding the use of toxic
reagents and catalysts, making this method very biofriendly.
Since NCL is a very specific ligation between N-terminal
cysteines and thioesters, side reactions with biomolecules
can be ruled out and therefore NCL is expected to be highly
compatible with encapsulated drugs. In this study, native
chemical ligation (NCL) was used as a selective crosslinking
method to form core-crosslinked thermosensitive polymeric
micelles for drug delivery applications. To this end, two ABA
triblock copolymers consisting of polyethylene glycol (PEG)
as midblock and thermosensitive poly isopropylacrylamide
(PNIPAM) outer blocks decorated with either cysteine (NIPAM-
co-HPMA-Cys)-PEG-P(NIPAM-co-HPMA-Cys) (PNC) or
thioester P(NIPAM-co-HPMA-ETSA)-PEG-P(NIPAM-co-HPMA-
ETSA) (PNE) functionalities were synthesized by atom transfer
radical polymerization (ATRP). Mixing of these polymers
in aqueous solution followed by heating to 50ºC resulted
in the formation of thermosensitive flower-like micelles.
Subsequently, native chemical ligation in the core of micelles
resulted in stabilization of the micelles with an average
diameter of 65 nm at 37°C. Decreasing the temperature to 10°C
only affected the size of the micelles (increased to 90 nm) but
hardly affected the polydispersity index (PDI) and aggregation
number (Nagg), confirming covalent stabilization of the micelles
by NCL. Notably, by simply adjusting the molar ratio between
the polymers, the extra cysteine or thioester moieties could be
used for conjugation of functional molecules. Furthermore, in
vitro cell experiments demonstrated that fluorescently labeled
micelles were successfully taken up by HeLa cells, while cell
viability remained high even at high micelle concentrations.
These results demonstrate the potential of these micelles for
drug delivery applications.
Biography
Tina Vermonden obtained her PhD in Physical and Organic Chemistry from
Wageningen University and Research Centre, and conducted her Post-doc-
toral training at Utrecht University. She is currently an Associate Professor in
the Department of Pharmaceutics at Utrecht University and Coordinator of
the Honours Program Pharmaceutical Sciences and is part of several large
national and EU consortia. Her research is focussed on the development
of biomaterials for tissue engineering and drug/protein delivery. Her group
designs, synthesizes and characterizes polymers with special emphasis on
cross-linking techniques to obtain advancedmaterial properties for biomed-
ical applications. His research interests are in the fields of Biomaterials, Hy-
drogels, Polymeric Micelles, Drug Delivery and Regenerative Medicine.
Core crosslinking of polymeric flower like micelles using native
chemical ligation
Tina Vermonden
Utrecht University, Netherlands
Tina Vermonden, Polym Sci, Volume 4
DOI: 10.4172/2471-9935-C1-008