Peptides have emerged as promising therapeutic molecules due to their high specificity, low toxicity and excellent oral bioavailability. Over the past few decades, numerous peptide drugs have been approved for clinical use and many more are currently in clinical trials. Some of the key approved peptide drugs include insulin, glucagon-like peptide-1 receptor agonists, calcitonin, oxytocin, exenatide and linaclotide that treat conditions like diabetes, osteoporosis, neuropathic pain etc.

Applications of peptide therapeutics

Cancer: Several peptide vaccine and immunotherapy approaches are being evaluated for cancer. Some exciting examples include PCV/PH20 vaccine in prostate cancer, hTERT long peptide vaccine in multiple cancers and NK cell engager BiSKIT in lymphoma. Peptides also show promise as targeted cancer cell-penetrating carriers to deliver toxic payloads.

Metabolic diseases: Incretin mimetic peptides like liraglutide and semaglutide are revolutionizing diabetes management. Other peptides in development target obesity, non-alcoholic steatohepatitis and fatty liver disease. Therapeutic peptides may provide safer, cost-effective alternatives to biologics.

Neurological disorders: Cell-penetrating peptides show potential to deliver biologics across the blood-brain barrier for disorders like Alzheimer's, Parkinson's, stroke and brain cancer. Ion channel modulating peptides are being explored for neuropathic pain, migraine and epilepsy.

Inflammation and fibrosis: Antifibrotic peptides hold promise for liver, lung and kidney fibrosis. Natriuretic peptides regulate blood pressure and fluid volumes. C3a/C5a receptor antagonists and other immunomodulatory peptides are being evaluated for inflammatory diseases.

Delivery and formulation advancements

One of the major challenges with peptide drugs has been their short plasma half-life due to rapid clearance and enzymatic degradation. Great progress has been made in optimizing Peptide Therapeutics formulation, conjugation and route of administration:

Prolonged-release formulations: Formulations like microspheres, nanoparticles, liposomes, hydrogels provide controlled release of peptides over hours to days, extending therapeutic activity without frequent dosing.

Modified amino acids: Replacing standard amino acids with D-amino acids, non-natural amino acids or cyclizing peptides enhances metabolic stability without affecting biological activity.

Conjugation strategies: Fusing peptides to larger carrier molecules like albumin, polymers, antibodies enhances molecular size and circulation time. Alternative routes like oral, transdermal and inhalation further improve delivery.

Technologies like peptide drug conjugates allow peptides to target receptors/tissues specifically and trigger release intracellularly, addressing bioavailability challenges. These developments will allow numerous safe and effective peptide candidates to reach patients.

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