title: In Vivo Imaging of the Stability and Sustained Cargo Release of an Injectable Amphipathic Peptide-Based Hydrogel.
abstract: Hydrogels are promising materials for biomedical applications such as tissue engineering and controlled drug release. In the past two decades, the peptide hydrogel subclass has attracted an increasing level of interest from the scientific community because of its numerous advantages, such as biocompatibility, biodegradability, and, most importantly, injectability. Here, we report on a hydrogel consisting of the amphipathic hexapeptide H-FEFQFK-NH2, which has previously shown promising in vivo properties in terms of releasing morphine. In this study, the release of a small molecule, a peptide, and a protein cargo as representatives of the three major drug classes is directly visualized by in vivo fluorescence and nuclear imaging. In addition, the in vivo stability of the peptide hydrogel system is investigated through the use of a radiolabeled hydrogelator sequence. Although it is shown that the hydrogel remains present for several days, the largest decrease in volume takes place within the first 12 h of subcutaneous injection, which is also the time frame wherein the cargos are released. Compared to the situation in which the cargos are injected in solution, a prolonged release profile is observed up to 12 h, showing the potential of our hydrogel system as a scaffold for controlled drug delivery. Importantly, this study elucidates the release mechanism of the peptide hydrogel system that seems to be based on erosion of the hydrogel providing a generally applicable controlled release platform for small molecule, peptide, and protein drugs.
authors.affiliation: Research Group of Organic Chemistry, Vrije Universiteit Brussel , Pleinlaan 2, 1050 Brussels, Belgium.|Research Group of Physical Chemistry and Polymer Science, Vrije Universiteit Brussel , Pleinlaan 2, 1050 Brussels, Belgium.|Supramolecular Chemistry Group, Department of Organic and Macromolecular Chemistry, Ghent University , Krijgslaan 281-S4, 9000 Ghent, Belgium.
authors.forename: Edith
authors.initials: E
authors.lastname: Oyen
authors.affiliation: Research Group of Organic Chemistry, Vrije Universiteit Brussel , Pleinlaan 2, 1050 Brussels, Belgium.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Martin
authors.affiliation: In Vivo Cellular and Molecular Imaging, Vrije Universiteit Brussel , Laarbeeklaan 103, 1090 Brussels, Belgium.
authors.forename: Vicky
authors.initials: V
authors.lastname: Caveliers
authors.affiliation: Organic and Biomimetic Chemistry Research Group, Department of Organic and Macromolecular Chemistry, Ghent University , Krijgslaan 281-S4, 9000 Ghent, Belgium.
authors.forename: Annemieke
authors.identifier: 0000-0003-0179-7608
authors.initials: A
authors.lastname: Madder
authors.affiliation: Research Group of Physical Chemistry and Polymer Science, Vrije Universiteit Brussel , Pleinlaan 2, 1050 Brussels, Belgium.
authors.forename: Bruno
authors.initials: B
authors.lastname: Van Mele
authors.affiliation: Supramolecular Chemistry Group, Department of Organic and Macromolecular Chemistry, Ghent University , Krijgslaan 281-S4, 9000 Ghent, Belgium.
authors.forename: Richard
authors.identifier: 0000-0001-7398-2058
authors.initials: R
authors.lastname: Hoogenboom
authors.affiliation: In Vivo Cellular and Molecular Imaging, Vrije Universiteit Brussel , Laarbeeklaan 103, 1090 Brussels, Belgium.
authors.forename: Sophie
authors.initials: S
authors.lastname: Hernot
authors.affiliation: Research Group of Organic Chemistry, Vrije Universiteit Brussel , Pleinlaan 2, 1050 Brussels, Belgium.
authors.forename: Steven
authors.identifier: 0000-0003-4123-1641
authors.initials: S
authors.lastname: Ballet
mesh_terms: D000818:Animals; D003692:Delayed-Action Preparations / Q000737:chemistry*; D016503:Drug Delivery Systems; D020100:Hydrogels / Q000737:chemistry*; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D010455:Peptides / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D011487:Protein Conformation; D055550:Protein Stability
chemical_list: D003692:Delayed-Action Preparations; D020100:Hydrogels; D010455:Peptides; D011092:Polyethylene Glycols