Strategies for overcoming protein and peptide instability in biodegradable drug delivery systems

The global pharmaceutical market has recently shifted its focus from small molecule drugs to peptide, protein, and nucleic acid drugs, which now comprise a majority of the top-selling pharmaceutical prod-ucts on the market. Although these biologics often offer improved drug specificity, new mechanisms of action, and/or enhanced efficacy, they also present new challenges, including an increased potential for degradation and a need for frequent administration via more invasive administration routes, which can limit patient access, patient adherence, and ultimately the clinical impact of these drugs. Controlled-release systems have the potential to mitigate these challenges by offering superior control over in vivo drug levels, localizing these drugs to tissues of interest (e.g., tumors), and reducing adminis-tration frequency. Unfortunately, adapting controlled-release devices to release biologics has proven dif-ficult due to the poor stability of biologics. In this review, we summarize the current state of controlled -release peptides and proteins, discuss existing techniques used to stabilize these drugs through encapsu-lation, storage, and in vivo release, and provide perspective on the most promising opportunities for the clinical translation of controlled-release peptides and proteins.& COPY; 2023 Elsevier B.V. All rights reserved.

Automated summary

The global pharmaceutical market has seen a shift in focus towards peptide, protein, and nucleic acid drugs, which now dominate the top-selling pharmaceutical products. While these biologics offer advantages such as improved drug specificity and enhanced efficacy, they also pose challenges including increased degradation and the need for frequent administration via invasive routes. Controlled-release systems have the potential to address these challenges by providing better control over drug levels, targeting specific tissues, and reducing administration frequency. However, adapting controlled-release devices for biologics has proven challenging due to their poor stability.