Strategies for Loading and Releasing Peptide Therapeutics in Biodegradable Carriers

ABSTRACT Peptides have become an increasingly important therapeutic modality for diverse diseases (e.g., diabetes and cancer) due to their high potency and specificity, favorable safety profiles, and improved manufacturability. Biodegradable micro‐ and nano‐carriers have consequently been widely investigated to protect peptides from enzymatic degradation and rapid systemic clearance while enabling sustained delivery. Despite substantial progress, biodegradable carrier–based peptide delivery remains limited by several persistent challenges: (i) low peptide loading capacity, (ii) an inherent trade‐off between high loading and suppression of initial burst release, and (iii) pronounced peptide‐to‐peptide variability in loading and release arising from heterogeneous physicochemical properties (e.g., charge, hydrophilicity, and solubility). To present insights for overcoming these unresolved issues, we aim to review recent strategies for efficiently loading and releasing peptide therapeutics in biodegradable carriers. After briefly introducing the properties and types of peptides and biodegradable carriers, the major limitations of biodegradable carrier‐based peptide delivery are meticulously discussed. Then, the potential solutions to resolve the limitations are presented based on the recently progressed works. Finally, we outline remaining knowledge gaps and future directions for scalable manufacturing, longer‐duration release, and clinical translation of biodegradable carrier‐based peptide delivery systems.