The effect of protein structure on their controlled release from an injectable peptide hydrogel.
Hydrogel materials are promising vehicles for the delivery of protein therapeutics. Proteins can impart physical interactions, both steric and electrostatic in nature, that influence their release from a given gel network. Here, model proteins of varying hydrodynamic diameter and charge are directly encapsulated and their release studied from electropositive fibrillar hydrogels prepared from the self-assembling peptide, MAX8. Hydrogelation of MAX8 can be triggered in the presence of proteins for their direct encapsulation with neither effect on protein structure nor the hydrogel's mechanical properties. Bulk release of the encapsulated proteins from the hydrogels was assessed for a month time period at 37 °C before and after syringe delivery of the loaded gels to determine the influence of the protein structure on release. Release of positively charged and neutral proteins was largely governed by the sterics imposed by the network. Conversely, negatively charged proteins interacted strongly with the positively charged fibrillar network, greatly restricting their release to <10% of the initial protein load. Partition and retention studies indicated that electrostatic interactions dictate the amount of protein available for release. Importantly, when protein encapsulated gels were delivered via syringe, the release profiles of the macromolecules show the similar trends as those observed for non-sheared gels. This study demonstrates that proteins can be directly encapsulated in self assembled MAX8 hydrogels, which can then be syringe delivered to a site where subsequent release is controlled by protein structure.
Chemical Biology Laboratory, National Cancer Institute, Frederick, MD 21701, USA.
Monica C
MC
Branco
Darrin J
DJ
Pochan
Norman J
NJ
Wagner
Joel P
JP
Schneider
D000818:Animals; D002942:Circular Dichroism; D003692:Delayed-Action Preparations / Q000008:administration & dosage*; D004058:Diffusion; D006801:Humans; D057446:Hydrodynamics; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007267:Injections; D008970:Molecular Weight; D010455:Peptides / Q000737:chemistry*; D011506:Proteins / Q000008:administration & dosage* / Q000737:chemistry*; D013997:Time Factors
D003692:Delayed-Action Preparations; D010455:Peptides; D011506:Proteins; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate