Polymer-based microencapsulation of peptidyl drugs: from bench to bedside

Peptides and proteins are the fastest-growing class of therapeutics due to their high specificity and potency. However, their widespread use is limited by enzymatic degradation, short circulation half-lives, and poor stability during storage and administration. Microencapsulation has emerged as a potential strategy in overcoming these barriers by protecting biomolecules, enabling sustained and targeted release, and improving patient compliance. This review highlights both natural and synthetic polymers, such as poly (lactic-co-glycolic acid) (PLGA), chitosan, alginate, and hybrid systems in terms of encapsulation efficiency, release kinetics, and clinical safety. Marketed products, including Lupron Depot®, Sandostatin LAR®, and Bydureon®, are discussed as successful examples of regulatory-approved microsphere formulations. Furthermore, emerging trends such as stimuli-responsive and multifunctional microspheres are presented as future directions that may lead to personalized and precision medicine. By integrating insights from marketed products and ongoing innovations, this review provides an updated framework for the design and development of peptide- and protein-based microencapsulation systems with the potential to enter therapeutic applications and improve clinical outcomes.