There are many proteins approved by the Federal Food and Drug Administration for use as therapeutics in humans. These proteins treat a variety of diseases. Many of them, however, are unstable and readily degrade upon storage. We have approached this problem in several ways. One of them is to develop polymers with side chain trehalose units that can be added or conjugated to proteins in order to stabilize them. The backbone and side chain can be varied and the polymer still stabilizes proteins effectively. These polymers can also be made as a copolymer with trehalose and pyridyl disulfide side chains. These polymers readily form nanoparticles. Proteins and peptides can be incorporated noncovalently or utilized as cross-linkers. In one example we modified the therapeutic peptide, glucagon to contain two thiols. This peptide was an effective cross-linker to form trehalose nanoparticles. The trehalose nanoparticles stabilized the glucagon and released the bioactive peptide upon reduction (Figure 1). This and other strategies to form nanoparticles and stabilize proteins will be discussed.

Nanoparticles to stabilize and release therapeutic proteins and peptides

2019 Fall National Meeting

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