UV-mediated thiol-ene click reactions for the synthesis of drug-loadable and degradable gels based on copoly(2-oxazoline)s.
An 80-membered library of gels composed of monofunctional 2-ethyl-2-oxazoline and 2-nonyl-2-oxazoline and one of four selected difunctional 2-oxazolines (containing either ether or ester bonds) were synthesized by microwave-assisted ring-opening polymerizations. The difunctional 2-oxazolines were prepared from the thiol-ene reaction of glycol dimercaptoacetate or 2,2'-(ethylenedioxy)diethanethiol and 2-but-3'-enyl-2-oxazoline or 2-dec-9'-enyl-2-oxazoline. 53 of the gels exhibited glass-transition temperatures, which ranged from -5.9 to 45.3 °C. 13 Derivatives exhibited glass-transition temperatures in the range from 20 to 30 °C, which renders them stiff at room temperature and flexible at body temperature. The gels that did not contain any 2-ethyl-2-oxazoline acted as lipogels, whereas the gels that did not contain any 2-nonyl-2-oxazoline acted as hydrogels; all other gels may be classified as amphigels. The swelling degrees were measured by gravimetry and maximum swelling degrees of 6 (in water) were observed for the gels with the lowest degrees of crosslinking. In a second approach, the synthesis of crosslinked networks had been achieved by performing the polymeranalogous thiol-ene reaction of copoly(2-oxazoline)s containing olefinic side-chains and glycol dimercaptoacetate. This soft strategy enabled the straightforward loading of such gels with active pharmaceutical ingredients without altering them. This method delivered gels with selected composition exhibiting a targeted disc-shape and loaded with active pharmaceutical ingredients from one-step syntheses. The maximum swelling degrees of these specimens were found to be in accordance with the ones from the first route investigated. Preliminary degradation studies were performed at 25 °C; these types of gels were found to be degraded in alkaline media as well as by esterases.
Polymer Competence Center Leoben, Roseggerstrasse 12, 8700 Leoben, Austria; Institute for Chemistry and Technology of Materials, Graz University of Technology, NAWI Graz, Stremayrgasse 9, 8010 Graz, Austria.
Klaus P
KP
Luef
IPREM, UMR 5254 UPPA/CNRS, Hélioparc, 2 Avenue Du Président Angot, 64053 Pau CEDEX 09, France.
Charlotte
C
Petit
Polymer Competence Center Leoben, Roseggerstrasse 12, 8700 Leoben, Austria.
Bettina
B
Ottersböck
Polymer Competence Center Leoben, Roseggerstrasse 12, 8700 Leoben, Austria.
Gernot
G
Oreski
IPREM, UMR 5254 UPPA/CNRS, Hélioparc, 2 Avenue Du Président Angot, 64053 Pau CEDEX 09, France.
Francis
F
Ehrenfeld
IPREM, UMR 5254 UPPA/CNRS, Hélioparc, 2 Avenue Du Président Angot, 64053 Pau CEDEX 09, France.
Bruno
B
Grassl
IPREM, UMR 5254 UPPA/CNRS, Hélioparc, 2 Avenue Du Président Angot, 64053 Pau CEDEX 09, France.
Stéphanie
S
Reynaud
Polymer Competence Center Leoben, Roseggerstrasse 12, 8700 Leoben, Austria.
Frank
F
Wiesbrock
Crosslinked network; Glass-transition temperature; Hydrogel; Poly(2-oxazoline); Swelling degree; Thiol-ene click reaction