title: Enzymatically cross-linked injectable alginate-g-pyrrole hydrogels for neovascularization.
abstract: Microparticles capable of releasing protein drugs are often incorporated into injectable hydrogels to minimize their displacement at an implantation site, reduce initial drug burst, and further control drug release rates over a broader range. However, there is still a need to develop methods for releasing drug molecules over extended periods of time, in order to sustain the bioactivity of drug molecules at an implantation site. In this study, we hypothesized that a hydrogel formed through the cross-linking of pyrrole units linked to a hydrophilic polymer would release protein drugs in a more sustained manner, because of an enhanced association between cross-linked pyrrole groups and the drug molecules. To examine this hypothesis, we prepared hydrogels of alginate substituted with pyrrole groups, alginate-g-pyrrole, through a horse-radish peroxidase (HRP)-activated cross-linking of the pyrrole groups. The hydrogels were encapsulated with poly(lactic-co-glycolic acid) (PLGA) microparticles loaded with vascular endothelial growth factor (VEGF). The resulting hydrogel system released VEGF in a more sustained manner than Ca(2+) alginate or Ca(2+) alginate-g-pyrrole gel systems. Finally, implantations of the VEGF-releasing HRP-activated alginate-g-pyrrole hydrogel system on chicken chorioallantoic membranes resulted in the formation of blood vessels in higher densities and with larger diameters, compared to other control conditions. Overall, the drug releasing system developed in this study will be broadly useful for regulating release rates of a wide array of protein drugs, and further enhance the quality of protein drug-based therapies.
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, 114 Roger Adams Laboratory, 600 S. Mathews Ave., Urbana 61801, USA.
authors.forename: Ross
authors.initials: R
authors.lastname: DeVolder
authors.affiliation: Department of Bioengineering, University of Illinois at Urbana-Champaign, 114 Roger Adams Laboratory, 600 S. Mathews Ave., Urbana 61801, USA.
authors.forename: Eleni
authors.initials: E
authors.lastname: Antoniadou
authors.affiliation: Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, 114 Roger Adams Laboratory, 600 S. Mathews Ave., Urbana 61801, USA. Electronic address: hjkong06@illinois.edu.
authors.forename: Hyunjoon
authors.initials: H
authors.lastname: Kong
mesh_terms: D000464:Alginates / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002645:Chickens; D049033:Chorioallantoic Membrane / Q000098:blood supply; D003432:Cross-Linking Reagents / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000378:metabolism; D020723:Glucuronic Acid / Q000737:chemistry / Q000378:metabolism; D006603:Hexuronic Acids / Q000737:chemistry / Q000378:metabolism; D020100:Hydrogels / Q000737:chemistry* / Q000378:metabolism; D007267:Injections; D019344:Lactic Acid / Q000737:chemistry; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011758:Pyrroles / Q000737:chemistry* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000464:Alginates; D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D006603:Hexuronic Acids; D020100:Hydrogels; D011758:Pyrroles; D042461:Vascular Endothelial Growth Factor A; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D020723:Glucuronic Acid
keywords: Alginate; Angiogenesis; Hydrogel; Protein delivery; Pyrrole; Sustained release