Engineering electrostatic interactions between a model osteogenic peptide and gelatin microparticles may extend soluble peptide release for several weeks.
In an in vitro study, researchers used thiolated gelatin microparticles fabricated from positively charged (type A) and negatively charged (type B) gelatin to evaluate whether electrostatic interactions could improve the sustained delivery of soluble peptides. They varied the charge of the gelatin carrier, the charge of peptides conjugated to the carrier, and the charge of peptide sequences attached to a model osteogenic growth peptide. The researchers examined peptide loading and release kinetics over 28 days, microparticle swelling and degradation, peptide conjugation efficiency, confocal imaging of peptide distribution, the effect of charge density on loading and release, and cytocompatibility.
The charge of the associating peptide and the gelatin carrier dictated peptide loading and release kinetics, whereas the charge of the conjugating peptide did not significantly affect peptide loading. Positive charge modification of the model peptide enabled controlled release for approximately 14 to 21 days through noncovalent electrostatic interactions.
Altering the charge of the conjugating peptide did not significantly affect swelling and had little effect on degradation. Similarly, conjugating peptide charge had minimal influence on peptide loading, whereas the charge of the associating peptide and the gelatin carrier consistently influenced loading and release behavior.
Positively charged peptide variants demonstrated the greatest loading to the gelatin microparticles. Positive charge modification also reduced the initial burst release compared with unmodified peptide when electrostatic attraction between the peptide and carrier was favored. Increasing the number of charged residues beyond four reduced peptide loading and increased burst release, suggesting that greater charge density did not further improve sustained delivery.
Release of the unmodified peptide did not differ substantially between phosphate-buffered saline and collagenase-containing conditions. In contrast, positive charge modification produced sustained release that paralleled microparticle degradation over about 2 to 3 weeks. Confocal microscopy demonstrated peptide distribution throughout the gelatin microparticles during the release period.
The study's limitations included that it was conducted entirely in vitro using a model osteogenic peptide and gelatin microparticle platform, limiting generalizability to other peptides or clinical applications. The researchers noted possible fluorescence interference from degrading microparticles, evaluation of blank particle controls only at baseline during imaging, variability related to particle size, and dose-dependent cytotoxicity of highly positively charged peptides at higher concentrations.
Electrostatic interactions may provide a tunable strategy for extending soluble peptide delivery from hydrogel systems.
"These noncovalent charge interactions can be harnessed to extend the release of peptides from hydrogel systems for drug delivery and tissue engineering applications," wrote lead study author Emily Y. Jiang, of the Department of Bioengineering at Rice University, and colleagues.
The study authors reported no conflicts of interest.
Source: Cell Biomaterials
