3d and 4d Printing Technologies in Personalized Drug Delivery Systems: Recent Advances, Challenges, and Future Perspectives

Personalized medicine is transforming healthcare by shifting from the conventional “one-size-fits-all” approach toward patient-specific therapeutic strategies. However, traditional pharmaceutical manufacturing systems have limited flexibility to produce individualized dosage forms that accommodate variations in patient age, body weight, genetic profile, disease severity, and metabolic characteristics. In recent years, additive manufacturing technologies, particularly three-dimensional (3D) and four-dimensional (4D) printing, have emerged as promising platforms for the development of personalized drug delivery systems. Three-dimensional printing enables the fabrication of customized pharmaceutical products with precise control over dosage, geometry, internal architecture, and drug release characteristics through layer-by-layer deposition of materials. Various printing techniques, including fused deposition modeling, stereolithography, selective laser sintering, inkjet printing, and semi-solid extrusion, have been extensively investigated for the development of oral dosage forms, transdermal systems, implantable devices, and pediatric formulations. Furthermore, four-dimensional printing extends the capabilities of conventional 3D printing by incorporating smart, stimuli-responsive materials that can undergo programmed transformations over time in response to environmental triggers such as temperature, pH, light, magnetic fields, moisture, and enzymes. These adaptive systems have demonstrated significant potential for site-specific and controlled drug delivery, tissue engineering, and regenerative medicine applications. Despite substantial progress, several challenges remain, including limited availability of printable biomaterials, manufacturing standardization, batch-to-batch reproducibility, stability concerns, regulatory uncertainties, and Good Manufacturing Practice compliance. The integration of artificial intelligence, digital healthcare technologies, and advanced biomaterials is expected to accelerate the clinical translation of these technologies. This review comprehensively summarizes recent advances in 3D and 4D printing technologies, their applications in personalized drug delivery, current manufacturing and regulatory challenges, and future perspectives for precision medicine. Overall, these emerging technologies have the potential to revolutionize pharmaceutical manufacturing by enabling safe, efficient, and patient-centered therapeutic interventions.