Shih, HanLin, Chien-Chi2017-08-242017-08-242015-07-13Shih, H., & Lin, C.-C. (2015). Photo-click hydrogels prepared from functionalized cyclodextrin and poly(ethylene glycol) for drug delivery and in situ cell encapsulation. Biomacromolecules, 16(7), 1915–1923. http://doi.org/10.1021/acs.biomac.5b00471https://hdl.handle.net/1805/13900Polymers or hydrogels containing modified cyclodextrin (CD) are highly useful in drug delivery applications, as CD is a cytocompatible amphiphilic molecule that can complex with a variety of hydrophobic drugs. Here, we designed modular photoclick thiol-ene hydrogels from derivatives of βCD and poly(ethylene glycol) (PEG), including βCD-allylether (βCD-AE), βCD-thiol (βCD-SH), PEG-thiol (PEGSH), and PEG-norbornene (PEGNB). Two types of CD-PEG hybrid hydrogels were prepared using radical-mediated thiol-ene photoclick reactions. Specifically, thiol-allylether hydrogels were formed by reacting multiarm PEGSH and βCD-AE, and thiol-norbornene hydrogels were formed by cross-linking βCD-SH and multiarm PEGNB. We characterized the properties of these two types of thiol-ene hydrogels, including gelation kinetics, gel fractions, hydrolytic stability, and cytocompatibility. Compared with thiol-allylether hydrogels, thiol-norbornene photoclick reaction formed hydrogels with faster gelation kinetics at equivalent macromer contents. Using curcumin, an anti-inflammatory and anticancer hydrophobic molecule, we demonstrated that CD-cross-linked PEG-based hydrogels, when compared with pure PEG-based hydrogels, afforded higher drug loading efficiency and prolonged delivery in vitro. Cytocompatibility of these CD-cross-linked hydrogels were evaluated by in situ encapsulation of radical sensitive pancreatic MIN6 β-cells. All formulations and cross-linking conditions tested were cytocompatible for cell encapsulation. Furthermore, hydrogels cross-linked by βCD-SH showed enhanced cell proliferation and insulin secretion as compared to gels cross-linked by either dithiothreitol (DTT) or βCD-AE, suggesting the profound impact of both macromer compositions and gelation chemistry on cell fate in chemically cross-linked hydrogels.en-USPublisher PolicyAttribution-NonCommercial-NoDerivs 3.0 United StatesAnimalsCell lineClick chemistryCurcumin -- pharmacokineticsCyclodextrins -- chemistryDrug delivery systems -- methodsHydrogels -- chemical synthesisHydrogels -- chemistryMicePolyethylene glycols -- chemistryArticle