Peptides are the fundamental building blocks of proteins. They are formed by short strings of amino acids (10–20 amino acids: oligopeptide; >20 amino acids: polypeptide), joined by sequential covalent bonds yielding peptide chains (1). Both naturally occurring and synthetic peptides can potentiate specific cellular functions and physiological processes that facilitate numerous biochemical processes in the body (1). Since the creation of the first medical-grade peptide (insulin) in 1921, many other peptide molecules have been discovered (1, 4). Current advances in drug development (e.g., recombinant display technologies, proteomics, genetic code expansion, new synthetic agents, venomics, and flexizymes) have led to a new era of therapeutic peptides with multiple medical uses (4, 5).
Between 2016 and 2022, the U.S. Food and Drug Administration approved 26 new peptide drugs (6). To date, >80 approved peptide agents are available for clinical therapies, including hormone mimetics (e.g., oxytocin and vasopressin) (7). Therapeutic development of peptides is situated between small molecules and biologics, accounting for about 5% of the global pharmaceutical market. Most approved peptide drugs are agonists, typically used in endocrinology, metabolism, and oncology (5). Furthermore, some peptide products are widely accessible to consumers as dietary supplements, which are largely unregulated. In 2015, therapeutic peptide products accounted for an estimated $35 billion industry, with a growth of 9% annually from 2016 to 2024 (8).
Peptide therapies are potential treatments for many chronic diseases, such as obesity, cancer, infectious diseases, and neuropsychiatric disorders (5, 8–10). In addition, cell-targeting and cell-penetrating peptides are promising therapeutic platforms for new treatments, including peptide agents acting as drug delivery vehicles (e.g., for antiviral, anticancer, or antibacterial medications) (2, 8).
Peptides have many physiological and pharmacological advantages (4, 5). They are essential biological mediators, exhibiting robust physiological potency and strength. In addition, they offer increased specificity compared with small molecules (5, 7). However, peptides also have important limitations, such as low systemic circulation time and reduced oral bioavailability due to rapid enzymatic degradation. In addition, peptide drugs tend to have a fast excretion rate, which means that parenteral administration is often recommended for these therapeutics (2, 5, 8).
Transdermal and pulmonary administrations have also been posited as possible delivery routes for peptides, and newer technological advances and emerging methodologies may help mitigate challenges with these delivery approaches.
