Electrosprayed PLGA Nanoparticles for Dual Drug Delivery: Design, Optimization and Applications

Poly(lactic-co-glycolic acid) (PLGA) is a biodegradable biopolymer widely used in advanced drug delivery systems (DDSs) due to its biocompatibility, controllable degradation behavior, and tunable physicochemical properties. Its degradation into naturally metabolized lactic and glycolic acids makes PLGA particularly attractive for biomedical applications, positioning PLGA nanoparticles as versatile carriers that bridge material design and therapeutic delivery. In this context, electrospray (electrohydrodynamic atomization) has emerged as an innovative and scalable processing technique that enables precise control over nanoparticle size, morphology, and internal structure under mild conditions, which is particularly suitable for engineering biopolymer-based DDSs. This review provides a comprehensive overview of electrospray-fabricated PLGA nanoparticles, with emphasis on the relationship between processing conditions, polymer structure, and functional performance. The fundamental mechanisms governing drug release, including diffusion, polymer degradation, and their combined effects, are discussed in relation to PLGA properties. The influence of electrospray parameters on nanoparticle formation, morphology, and internal architecture is analyzed, highlighting how process–structure–property relationships can be tailored to achieve specific release profiles. Structural design strategies, including single-matrix, core–shell, and surface-functionalized nanoparticles, are further examined as approaches to enable controlled and sequential dual-DDSs. In addition, emerging modeling and computational approaches are briefly discussed as complementary tools for understanding and optimizing nanoparticle behavior. Challenges and technical problems, such as substrates for nanoparticle detachment, are discussed.