Mechanistic Insights into Drug Release from PLGA- and PLA-Based Implants

Abstract Biodegradable polymer implants offer long-acting drug delivery, yet the roles of polymer chemistry and drug properties in governing release remain incompletely understood. We hypothesized that polymer viscosity and end-group chemistry regulate water uptake, glass-transition, and chain mobility, thereby controlling implant dissolution and drug release. To test this, drug-loaded implants were fabricated using PLGA and PLA polymers with varied inherent viscosities, lactide/glycolide ratios, and end-group chemistries via vacuum compression molding, and characterized using water-uptake studies, dissolution testing, and NMR analyses. Low-viscosity, acid-terminated polymers showed rapid water uptake and a marked reduction in glass-transition temperature, inducing a transition to a rubbery state with enhanced chain mobility. These changes accelerated implant dissolution and drug release. Drug solubility further modulated drug release: acetaminophen promoted fast dissolution, whereas dexamethasone exhibited slower, polymer-controlled release. The formulations demonstrated a clear in vitro−in vivo relationship, supporting their relevance for preclinical evaluation. Overall, the results establish how polymer chemistry, polymer mobility, and drug physicochemical properties collectively determine release performance, providing a mechanistic basis for designing biodegradable implants with tunable profiles.