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Peptide drugs are a highly diverse group of therapeutic agents. Over the last decade, more than 40 peptides have been approved for clinical use. They target different structures, ranging from G protein-coupled receptors (GPCRs) to pathogens and are used to treat a variety of indications, including metabolic disorders, genetic diseases, acute illnesses and more. Structurally, peptide therapeutics are a heterogeneous class. This diversity allows them to bridge the gap between small molecules and biologics. However, limited metabolic stability and bioavailability must be addressed. Strategies to improve the half-life include backbone and sequence modification, cyclization and the addition of stabilizing moieties. Great strides have been made in recent years towards achieving sufficient drug uptake for oral application have been achieved within recent years. However, these methods require specialized peptide design or involve permeabilization of the gastrointestinal tract. Consequently, other routes of administration are being explored. One promising approach is the nasal application of peptides. This method can be used for systemic uptake, but also allows for direct nose-to-brain delivery of compounds. While successful nose-to-brain delivery is already used in the clinic, the underlining mechanisms are poorly understood. Strategies for rational optimization are needed to make this method more applicable to a wider range of compounds. Overall, approved peptide therapeutics cover a wide range of applications and have demonstrated a growing and novel potential in recent drug discovery.
Jülke et al. (Fri,) studied this question.