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Polymer Chemistry 2018

Polymer Sciences

ISSN: 2471-9935

Page 34

March 26-28, 2018

Vienna, Austria

3

rd

Edition of International Conference and Exhibition on

Polymer Chemistry

N

ative 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 (N

agg

), 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.

[email protected]

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