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Nanomedicine is among the most promising emerging fields that can provide innovative and radical solutions to unmet needs in pharmaceutical formulation development. Encapsulation of active pharmaceutical ingredients within nano-size carriers offers several benefits, namely, protection of the therapeutic agents from degradation, their increased solubility and bioavailability, improved pharmacokinetics, reduced toxicity, enhanced therapeutic efficacy, decreased drug immunogenicity, targeted delivery, and simultaneous imaging and treatment options with a single system. Poly(lactide-co-glycolide) (PLGA) is one of the most commonly used polymers in nanomedicine formulations due to its excellent biocompatibility, tunable degradation characteristics, and high versatility. Furthermore, PLGA is approved by the European Medicines Agency (EMA) and the Food and Drug Administration (FDA) for use in pharmaceutical products. Nanomedicines based on PLGA nanoparticles can offer tremendous opportunities in the diagnosis, monitoring, and treatment of various diseases. This Special Issue aims to focus on the bench-to-bedside development of PLGA nanoparticles including (but not limited to) design, development, physicochemical characterization, scale-up production, efficacy and safety assessment, and biodistribution studies of these nanomedicine formulations.