Historical advancements in targeted nanoscale drug delivery systems

Abstract

This inclusive examination of the evolution of nanoscale drug delivery systems (DDSs) elucidates the profound impact these technologies have exerted on modern medicine. From the seminal development of liposomal encapsulation in the 1960s to contemporary advancements in polymeric micelles, dendrimer-based carriers, and CRISPR–Cas9 delivery vectors, the progression of nanotechnology has markedly enhanced therapeutic precision and efficacy. Notable innovations, particularly in oncological applications, include the deployment of polyethylene glycol conjugation and stimuli-responsive nanocarriers, which have substantially improved the stability, pharmacokinetic profiles, and targeted delivery of therapeutic agents. Nonetheless, several challenges persist, including the scale-up of manufacturing processes, batch-to-batch reproducibility, and biocompatibility and toxicity concerns. The incorporation of artificial intelligence (AI) and machine learning (ML) into nanoparticle design and optimization offers a promising avenue for overcoming these obstacles. AI and ML methodologies have the potential to expedite the discovery of novel nanocarriers formulations, predict biological interactions with high accuracy, and streamline the development pipeline. As these technologies evolve, they may facilitate ground breaking advancements in the treatment of complex diseases such as malignancies, genetic disorders, and chronic conditions. The future landscape of nanomedicine is poised to offer increasingly personalized, efficacious, and safe therapeutic options, with emerging innovations such as nanorobots and biodegradable nanomaterials anticipated to revolutionize therapeutic paradigms. Continued research into the biodegradability and biocompatibility of nanomaterials is expected to address current limitations, ensuring that these advanced DDSs are both effective and safe for clinical applications. The advent of “smart” nanocarriers capable of real-time monitoring and adaptive responses to physiological fluctuations could further enhance therapeutic precision and patient outcomes. The ongoing evolution of nanoscale DDSs is poised to drive significant advancements in precision medicine, transforming disease management strategies and heralding a new era of therapeutic possibilities. © 2026 Elsevier Inc. All rights reserved.