EVOLUTION OF DRUG DELIVERY SYSTEMS: TRANSITION FROM CONVENTIONAL FORMULATIONS TO SMART AND AI-ASSISTED DRUG DELIVERY

Drug delivery systems (DDS) have undergone remarkable evolution from conventional formulations to intelligent therapeutic platforms capable of achieving controlled, targeted, and personalized drug administration. Conventional dosage forms often exhibit limitations such as poor bioavailability, non-specific drug distribution, frequent dosing, and systemic adverse effects, thereby necessitating the development of advanced drug delivery technologies. This review systematically examines the evolution of DDS from conventional and controlled drug delivery systems to targeted, nanotechnology-based, stimuli-responsive smart drug delivery systems, and artificial intelligence (AI)-assisted drug delivery technologies. A comprehensive literature search was performed using major scientific databases, including PubMed, Scopus, Web of Science, ScienceDirect, and Google Scholar, together with relevant regulatory guidance documents published by the U.S. Food and Drug Administration (FDA), European Medicines Agency (EMA), International Council for Harmonisation (ICH), International Medical Device Regulators Forum (IMDRF), and the World Health Organization (WHO). Literature published primarily between 2000 and 2026 was critically evaluated based on relevance, scientific quality, and clinical significance. The review discusses the design principles, mechanisms, carrier materials, therapeutic applications, clinical status, advantages, and translational limitations of pH-, temperature-, enzyme-, redox-, magnetic-, light-, and ultrasound-responsive drug delivery systems. Furthermore, recent advances in AI-assisted formulation optimization, machine learning, digital twins, AI-enabled closed-loop drug delivery, and cyber security are highlighted as emerging technologies supporting precision and personalized medicine. Current scientific, manufacturing, regulatory, ethical, and cyber security challenges affecting the clinical translation of advanced drug delivery systems are also critically discussed. Overall, this review provides a comprehensive overview of the technological evolution of drug delivery systems while highlighting future opportunities for integrating smart biomaterials, nanotechnology, and AI to accelerate the development of safer, more effective, and patient-specific therapeutic platforms.