title: Photoclick Hydrogels Prepared from Functionalized Cyclodextrin and Poly(ethylene glycol) for Drug Delivery and in Situ Cell Encapsulation.
abstract: Polymers 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.
authors.affiliation: †Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 47907, United States.
authors.forename: Han
authors.initials: H
authors.lastname: Shih
authors.affiliation: †Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana 47907, United States.|‡Department of Biomedical Engineering, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana 46202, United States.
authors.forename: Chien-Chi
authors.initials: CC
authors.lastname: Lin
mesh_terms: D000818:Animals; D002460:Cell Line; D057930:Click Chemistry; D003474:Curcumin / Q000493:pharmacokinetics; D003505:Cyclodextrins / Q000737:chemistry*; D016503:Drug Delivery Systems / Q000379:methods; D020100:Hydrogels / Q000138:chemical synthesis* / Q000737:chemistry; D051379:Mice; D011092:Polyethylene Glycols / Q000737:chemistry*
chemical_list: D003505:Cyclodextrins; D020100:Hydrogels; D011092:Polyethylene Glycols; D003474:Curcumin