Peptide cargo administration: current state and applications

Effective delivery of drug molecules to the target site is a challenging task. In the last decade, several innovations in the drug delivery system (DDS) have tremendously improved the therapeutic efficacy of drug molecules. Among various DDS, cell-penetrating peptides (CPPs) based DDS have gathered notable attention owing to their safety, efficacy, selectivity, specificity, and ease of synthesis. CPPs are emerging as an efficient and effective pharmaceutical nanocarriers-based platforms for successful management of various important human health disorders. Failure of several current chemotherapeutic strategies is attributed to low solubility, reduced bioavailability, and off-target delivery of several anti-cancer drugs. Similarly, development of therapeutics for vision-threatening disorders is challenged by the anatomical as well as physiological complexity of the eye. Such therapeutic challenges in cancer and ocular disease management can be overcome by developing cell-penetrating peptide (CPP) based peptide drug conjugates (PDCs). CPPs can be used to deliver various types of cargo molecules including nucleic acids, small molecules, and peptides/proteinaceous agents. In this review, we have briefly introduced CPPs and the linker strategies employed for the development of PDCs. Furthermore, recent studies employing CPP-based PDCs for cancer and ocular disease management have been discussed in detail highlighting their significance over conventional DDS. Later sections of the review are focused on the current status of clinical trials and future implications of CPP-based PDCs in vaccine development. KEY POINTS: • Cell-penetrating peptides (CPPs) can deliver a variety of cargo macromolecules via covalent and non-covalent conjugation. • CPP-based peptide drug conjugates (PDCs) can overcome drawbacks of conventional drug delivery methods such as biocompatibility, solubility, stability, and specificity. • Various PDCs are in clinical trial phase for cancer and ocular therapeutics.