TY - JOUR
T1 - Enzymatically cross-linked injectable alginate-g-pyrrole hydrogels for neovascularization
AU - Devolder, Ross
AU - Antoniadou, Eleni
AU - Kong, Hyunjoon
N1 - Funding Information:
This work was supported by the National Science Foundation ( CAREER: DMR-0847253 and Emerging Behaviors in Integrated Cellular Systems Grant: CBET-0939511 to H.J.K.) and the National Institute of Health ( 1R25CA154015A ) (R.D.). The authors also wish to thank Mr. Frank Rauh (FMC BioPolymer) for the supply of alginate.
PY - 2013
Y1 - 2013
N2 - 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 Ca2 + 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.
AB - 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 Ca2 + 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.
KW - Alginate
KW - Angiogenesis
KW - Hydrogel
KW - Protein delivery
KW - Pyrrole
KW - Sustained release
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U2 - 10.1016/j.jconrel.2013.07.010
DO - 10.1016/j.jconrel.2013.07.010
M3 - Article
C2 - 23886705
AN - SCOPUS:84883523733
SN - 0168-3659
VL - 172
SP - 30
EP - 37
JO - Journal of Controlled Release
JF - Journal of Controlled Release
IS - 1
ER -