Dataset Information

UV-mediated thiol-ene click reactions for the synthesis of drug-loadable and degradable gels based on copoly(2-oxazoline)s.

ABSTRACT: 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.

SUBMITTER: Luef KP

PROVIDER: S-EPMC5349497 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

UV-mediated thiol-ene click reactions for the synthesis of drug-loadable and degradable gels based on copoly(2-oxazoline)s.

Luef Klaus P KP Petit Charlotte C Ottersböck Bettina B Oreski Gernot G Ehrenfeld Francis F Grassl Bruno B Reynaud Stéphanie S Wiesbrock Frank F

European polymer journal 20160820

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-transitio ...[more]

PMID: 28316339

Similar Datasets

Project description:Hydrogels with dynamically tunable crosslinking are invaluable for directing stem cell fate and mimicking a stiffening matrix during fibrosis or tumor development. The increases in matrix stiffness during tissue development are often accompanied by the accumulation of extracellular matrices (e.g., collagen, hyaluronic acid (HA)), a phenomenon that has received little attention in the development of dynamic hydrogels. In this contribution, we present a gelatin-based cell-laden hydrogel system capable of being dynamically stiffened while accumulating HA, a key glycosaminoglycans (GAG) increasingly deposited by stromal cells during tumor progression. Central to this strategy is the synthesis of a dually-modified gelatin macromer - gelatin-norbornene-carbohydrazide (GelNB-CH), which is susceptible to both thiol-norbornene photopolymerization and hydrazone click chemistry. We demonstrate that the crosslinking density of cell-laden thiol-norbornene hydrogels can be dynamically tuned via simple incubation with aldehyde-bearing macromers (e.g., oxidized dextran (oDex) or oHA). The GelNB-CH hydrogel system is highly cytocompatible, as demonstrated by in situ encapsulation of pancreatic cancer cells (PCC) and cancer-associated fibroblasts (CAF). This unique dynamic stiffening scheme provides a platform to study tandem accumulation of HA and elevation in matrix stiffness in the pancreatic tumor microenvironment. STATEMENT OF SIGNIFICANCE: Hydrogels permitting on-demand and secondary crosslinking are ideal for mimicking a stiffening tumor microenvironment (TME). However, none of the current dynamic hydrogels account for both stiffening and accumulation of hyaluronic acid (HA), a major extracellular matrix component increasingly deposited in tumor stromal tissues, including pancreatic ductal adenocarcinoma (PDAC). The current work addresses this gap by developing a dynamic hydrogel system capable of simultaneously increasing stiffness and HA accumulation. This is achieved by a new gelatin macromer permitting sequential thiol-norbornene (for primary network crosslinking) and hydrazone click chemistry (for bioinert or biomimetic stiffening with oxidized dextran (oDex) or oHA, respectively). The results of this study provide new insights into how dynamically changing physicochemical matrix properties guide cancer cell fate processes.

Dataset Information

UV-mediated thiol-ene click reactions for the synthesis of drug-loadable and degradable gels based on copoly(2-oxazoline)s.

Publications

UV-mediated thiol-ene click reactions for the synthesis of drug-loadable and degradable gels based on copoly(2-oxazoline)s.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets