Rice University engineers have developed a new strategy for controlling how therapeutic peptides are released from gelatin-based materials, according to an Aug. 7 announcement. This development could improve the use of these molecules in tissue engineering and drug delivery.
Peptides can encourage biological processes such as bone formation, blood vessel growth, and tissue repair. While their small size makes them more stable and easier to manufacture than larger proteins, it also presents a challenge: peptides often diffuse out of water-rich materials like hydrogels too quickly to be effective at treatment sites.
In a study published in Cell Biomaterials, Rice engineers led by Antonios Mikos, the Louis Calder Professor of Bioengineering and Chemical and Biomolecular Engineering, worked with researchers at Kyoto University to address this issue. They adjusted the electrical charge of both a model bone-promoting peptide and the gelatin microparticles used as carriers. The team found that electrostatic attraction between oppositely charged peptides and gelatin could slow release for up to two or three weeks.
The research focused on osteogenic growth peptide (OGP), associated with bone formation. Researchers modified OGP by adding sequences of charged amino acids, creating versions with positive, negative, or balanced charges before loading them into gelatin microparticles. Gelatin was chosen for its biocompatibility and variable electrical charge properties.
The results indicated that modifying the peptide's charge had the greatest effect on retention within the particles and reduced initial burst release when placed in liquid environments. The carrier's charge also influenced delivery, but adding extra charged sequences directly to gelatin had limited impact on swelling or degradation.
Emily Jiang, first author of the study and doctoral student in Mikos' lab, said: "This study demonstrates that relatively simple charge modifications can provide a powerful way to tune peptide delivery... Because the peptide is held through noncovalent interactions rather than permanently attached to the carrier, it can still be released in its soluble form and potentially remain available to interact with surrounding cells and tissues." Mikos added: "This platform gives us several variables that can be adjusted to create a desired release profile... The broader goal is to develop adaptable delivery systems that can provide therapeutic peptides at the right location and over the right period of time for a particular regenerative application."