The goal of the project is to design new macromolecular structures, whose assembly into hybrid hydrogels will be modulated by association of coiled-coil peptide domains. N-(2-hydroxypropyl)rnethacrylamide (HPMA) copolymers containing coiled-coil domains as side-chains (grafts) will be synthesized by copolymerization of HPMA with macromonomers containing coiled-coils. The design of coiled-coil grafts imposes an antiparallel heterodimer formation in the self-assembly process. We hypothesize that the antiparallel orientation of heterodimers will contribute to the homogeneity of the self-assembled hybrid hydrogels due to the unique interchain dimer formation and decreased steric hindrance of the polymer backbone on the """"""""in-register"""""""" alignment of heterodimers. Materials with tailor-made structures at the nanometer range will result from the proposed research. A theoretical model will be developed to assist in a rational design of the hybrid hydrogels. Experimental results will be analyzed using the model to provide feedback for the optimization of graft copolymer structure and of the self-assembly into hybrid hydrogels. The self-assembly of HPMA graft copolymers in the presence of encapsulated molecules will be evaluated in an attempt to develop new in-situ forming hybrid hydrogels for the delivery of proteins. The delivery system is suitable for a wide variety of biological molecules since the self-assembly occurs in aqueous media. The new hydrogels may find wide-ranging biomedical applications in drug delivery, biosensors, affinity separations, and nanoreactors. In addition, the possibility to join non-compatible materials, such as hydrophobic muscle mimics from liquid crystalline polymers and hydrogels, may open a new field of research.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
5R01EB005288-03
Application #
7173402
Study Section
Special Emphasis Panel (ZRG1-GDD (01))
Program Officer
Henderson, Lori
Project Start
2005-04-01
Project End
2009-01-31
Budget Start
2007-02-01
Budget End
2008-01-31
Support Year
3
Fiscal Year
2007
Total Cost
$287,050
Indirect Cost
Name
University of Utah
Department
Pharmacology
Type
Schools of Pharmacy
DUNS #
009095365
City
Salt Lake City
State
UT
Country
United States
Zip Code
84112
Yang, Jiyuan; Kope?ek, Jind?ich (2016) Design of smart HPMA copolymer-based nanomedicines. J Control Release 240:9-23
Yang, Jiyuan; Kope?ek, Jind?ich (2015) POLYMERIC BIOMATERIALS AND NANOMEDICINES. J Drug Deliv Sci Technol 30:318-330
Yang, Jiyuan; Kope?ek, Jind?ich (2014) Macromolecular therapeutics. J Control Release 190:288-303
Kope?ek, Jind?ich (2013) Polymer-drug conjugates: origins, progress to date and future directions. Adv Drug Deliv Rev 65:49-59
Wu, Kuangshi; Yang, Jiyuan; Liu, Jihua et al. (2012) Coiled-coil based drug-free macromolecular therapeutics: in vivo efficacy. J Control Release 157:126-31
Johnson, Russell N; Kope?ková, Pavla; Kope?ek, Jind?ich (2012) Biological activity of anti-CD20 multivalent HPMA copolymer-Fab' conjugates. Biomacromolecules 13:727-35
Kope?ek, Jind?ich; Yang, Jiyuan (2012) Smart self-assembled hybrid hydrogel biomaterials. Angew Chem Int Ed Engl 51:7396-417
Wu, Larisa C; Yang, Jiyuan; Kope?ek, Jind?ich (2011) Hybrid hydrogels self-assembled from graft copolymers containing complementary ?-sheets as hydroxyapatite nucleation scaffolds. Biomaterials 32:5341-53
Wu, Kuangshi; Liu, Jihua; Johnson, Russell N et al. (2010) Drug-free macromolecular therapeutics: induction of apoptosis by coiled-coil-mediated cross-linking of antigens on the cell surface. Angew Chem Int Ed Engl 49:1451-5
Kopecek, Jindrich (2010) Biomaterials and drug delivery: past, present, and future. Mol Pharm 7:922-5

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