Nanoparticles for Drug Delivery: Design, Mechanisms, and Clinical Translation

Nanoparticle-based drug delivery systems have become an important component of modern nanomedicine, enabling improved drug protection, controlled release, targeted delivery, and the modulation of pharmacokinetic behavior. Their therapeutic performance is governed by physicochemical properties such as size, shape, surface chemistry, and material composition, which influence biological interactions, biodistribution, cellular uptake, and clearance. This review examines major nanoparticle platforms, including polymeric, lipid-based, inorganic, carbon-based, and hybrid systems, together with passive and active targeting and endogenous and externally triggered release strategies. Current and emerging applications in oncology, infectious diseases, central nervous system disorders, gene therapy, and vaccines are discussed alongside theranostic and combination-delivery approaches. Particular emphasis is placed on computational modeling, artificial intelligence, and digital twins for formulation optimization and personalized nanomedicine. Key barriers to clinical translation, including manufacturing scalability, biological variability, limitations of EPR-mediated targeting, regulatory standardization, and long-term safety, are critically evaluated. Finally, emerging directions in sustainable nanomanufacturing and biomimetic delivery are discussed. By integrating biological mechanisms with computational, manufacturing, regulatory, and clinical considerations, this review provides a translational perspective on advancing nanoparticle drug-delivery systems from laboratory development toward clinical implementation.