Therapeutic peptides and proteins: Status and developments in drug delivery

Peptides and proteins are the most dynamic class of biomolecules, performing a diverse range of physiological functions including biochemical catalysis, ion transport, molecular signaling, and genetic/epigenetic regulation and expression. Considering their indispensable functionality and tremendous diversity, peptide and protein related diseases present both an enormous challenge to human health and a valuable opportunity for therapeutic development. Unfortunately, peptide and protein therapeutics are susceptible to proteolytic degradation and often exhibit poor membrane permeability. Moreover, renal clearance, short circulation time, low plasma stability, and immunogenicity are persistent challenges for delivery. Due to inherent lability in the GI tract and poor absorption and permeability through membranes, the majority of FDA-approved peptide and protein therapeutics are approved for parenteral delivery. However, molecular engineering, drug carriers, and/or co-formulations with effective agents may be used to enhance drug delivery and enable use of more attractive administration routes. This review catalogues and describes established and emerging strategies for chemical and structural modification, formulation, and administration of peptide and protein therapeutics, additionally analyzing how such strategies and technologies have influenced scientifically ground-breaking and commercially successful therapies in the modern market.