Translational Strategies in Smart Drug Delivery Systems for Controlled and Personalized Pharmacokinetics

Advancements in drug delivery systems (DDSs) have developed pharmacotherapy by enabling precise control over drug pharmacokinetics (PKs), enhancing therapeutic efficacy, minimizing toxicity, and improving patient compliance. This review comprehensively examines emerging DDS strategies designed to optimize absorption, distribution, metabolism, and excretion (ADME) of therapeutic agents. Key innovations include nanotechnology-based carriers (liposomes, polymeric nanoparticles, and dendrimers), stimuli-responsive and smart delivery systems, site-specific and tissue-targeted DDS, and prodrug DDS hybrid approaches. Integration of PK modeling, artificial intelligence (AI), and omics data has facilitated personalized and patient-specific therapy, while advanced computational tools allow predictive simulation of drug behavior. Translational challenges such as scale-up, regulatory approval, interpatient variability, long-term safety, and clinical trial design are discussed, alongside strategies to overcome these barriers. Future perspectives emphasize AI-assisted optimization, multimodal DDS combining therapeutic and diagnostic functionalities, biodegradable and sustainable materials, and regenerative and cellular delivery platforms. Collectively, these developments highlight a paradigm shift toward adaptive, precise, and personalized pharmacotherapy, bridging preclinical innovation with clinical application. This review provides a comprehensive framework for understanding the current landscape and future directions of DDS in controlling PKs, ultimately supporting safer and more effective patient-centric therapies.