title: Drug-triggered and cross-linked self-assembling nanofibrous hydrogels.
abstract: Self-assembly of multidomain peptides (MDP) can be tailored to carry payloads that modulate the extracellular environment. Controlled release of growth factors, cytokines, and small-molecule drugs allows for unique control of in vitro and in vivo responses. In this study, we demonstrate this process of ionic cross-linking of peptides using multivalent drugs to create hydrogels for sustained long-term delivery of drugs. Using phosphate, heparin, clodronate, trypan, and suramin, we demonstrate the utility of this strategy. Although all multivalent anions result in good hydrogel formation, demonstrating the generality of this approach, suramin led to the formation of the best hydrogels per unit concentration and was studied in greater detail. Suramin ionically cross-linked MDP into a fibrous meshwork as determined by scanning and transmission electron microscopy. We measured material storage and loss modulus using rheometry and showed a distinct increase in G' and G″ as a function of suramin concentration. Release of suramin from scaffolds was determined using UV spectroscopy and showed prolonged release over a 30 day period. Suramin bioavailability and function were demonstrated by attenuated M1 polarization of THP-1 cells compared to positive control. Overall, this design strategy has allowed for the development of a novel class of polymeric delivery vehicles with generally long-term release and, in the case of suramin, cross-linked hydrogels that can modulate cellular phenotype.
authors.affiliation: †Department of Chemistry and ‡Department of Bioengineering, Rice University, Mail Stop 602, 6100 Main Street, Houston, Texas 77030, United States.
authors.forename: Vivek A
authors.initials: VA
authors.lastname: Kumar
authors.affiliation: †Department of Chemistry and ‡Department of Bioengineering, Rice University, Mail Stop 602, 6100 Main Street, Houston, Texas 77030, United States.
authors.forename: Siyu
authors.initials: S
authors.lastname: Shi
authors.affiliation: †Department of Chemistry and ‡Department of Bioengineering, Rice University, Mail Stop 602, 6100 Main Street, Houston, Texas 77030, United States.
authors.forename: Benjamin K
authors.initials: BK
authors.lastname: Wang
authors.affiliation: †Department of Chemistry and ‡Department of Bioengineering, Rice University, Mail Stop 602, 6100 Main Street, Houston, Texas 77030, United States.
authors.forename: I-Che
authors.initials: IC
authors.lastname: Li
authors.affiliation: †Department of Chemistry and ‡Department of Bioengineering, Rice University, Mail Stop 602, 6100 Main Street, Houston, Texas 77030, United States.
authors.forename: Abhishek A
authors.initials: AA
authors.lastname: Jalan
authors.affiliation: †Department of Chemistry and ‡Department of Bioengineering, Rice University, Mail Stop 602, 6100 Main Street, Houston, Texas 77030, United States.
authors.forename: Biplab
authors.initials: B
authors.lastname: Sarkar
authors.affiliation: †Department of Chemistry and ‡Department of Bioengineering, Rice University, Mail Stop 602, 6100 Main Street, Houston, Texas 77030, United States.
authors.forename: Navindee C
authors.initials: NC
authors.lastname: Wickremasinghe
authors.affiliation: †Department of Chemistry and ‡Department of Bioengineering, Rice University, Mail Stop 602, 6100 Main Street, Houston, Texas 77030, United States.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Hartgerink
mesh_terms: D000818:Animals; D002460:Cell Line; D003692:Delayed-Action Preparations; D004337:Drug Carriers / Q000737:chemistry*; D065546:Drug Liberation; D005260:Female; D006801:Humans; D020100:Hydrogels / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D057139:Nanofibers / Q000737:chemistry*; D009842:Oligopeptides / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D051381:Rats
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D020100:Hydrogels; D009842:Oligopeptides; D004364:Pharmaceutical Preparations; C047981:arginyl-glycyl-aspartic acid
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