Comprehensive Review: Overcoming the Biggest Challenges with Peptide and Protein Drugs | Research

The takeaway

A critical review examines strategies including PEGylation, lipidation, nanoformulation, and novel delivery systems to overcome the instability, short half-life, and poor oral bioavailability of peptide drugs.

5 major challenges addressed
Instability, short half-life, poor oral bioavailability, and immunogenicity solutions reviewed

What the researchers found

Current strategies including PEGylation, lipidation, nanoformulation, and advanced delivery systems can effectively address the chemical instability, short half-life, and poor bioavailability of peptide drugs.

Why it matters

Peptide drugs are the fastest-growing drug class, but their limitations still restrict their potential. Understanding and overcoming these challenges is essential for the entire field.

How the study worked

Comprehensive literature review of peptide drug challenges and strategic solutions across multiple domains.

What this study cannot tell us

Review format — doesn't generate new data; some strategies work for specific peptides but not universally; cost and manufacturing complexity of advanced formulations.

How to read the evidence

Comprehensive review — authoritative summary of current knowledge and strategies.

When this study was published

Published in 2026, providing the most current overview of peptide drug engineering.

The bigger picture

This review provides a roadmap for the peptide drug industry — showing how engineering and formulation science are systematically solving each limitation that has historically restricted peptide therapeutics.

Questions still open

Will oral peptide delivery become routine in the next decade?
Can AI-driven peptide design avoid instability problems at the molecular design stage?

Common questions

Why are peptide drugs so challenging to develop?

Peptides are fragile — they break down in acid, are destroyed by enzymes, are cleared quickly by kidneys, and can trigger immune reactions. Each of these problems requires specific engineering solutions.

What is PEGylation?

PEGylation attaches polyethylene glycol (PEG) chains to peptide drugs, making them larger so they are cleared more slowly and protected from enzymes. It's one of the most successful strategies for extending peptide drug half-life.

Read the original research

Strategic Approaches for Overcoming Peptide and Protein Drug Limitations.

The protein journal, 45(1), 8-21

View on PubMed ↗Publisher’s paper ↗

Citation

Cheshomi, Mahsa; Shobeiri, Nikta; Tajani, Amineh Sadat; Khameneh, Bahman. (2026). Strategic Approaches for Overcoming Peptide and Protein Drug Limitations.. The protein journal, 45(1), 8-21. https://doi.org/10.1007/s10930-025-10302-8