Nanotechnology-driven smart drug delivery systems bridging pharmaceutical sciences biomaterials and clinical translation

Smart drug delivery systems (SDDS) powered by nanotechnology have emerged as a promising approach to overcome the main drawbacks of traditional medication administration, such as low bioavailability, non-targeted distribution, rapid clearance, and systemic toxicity. Nanocarrier-based platforms, including lipid-based, polymeric, inorganic, and hybrid types, possess tunable physicochemical characteristics that determine their pharmacokinetics and therapeutic performance. Nanocarriers can be stimulated by various internal stimuli, including pH, redox gradients, enzymes, and hypoxia, as well as external stimuli such as light, temperature, magnetic fields, and ultrasound. Subsequently, these nanocarriers can selectively release drugs at particular sites to permit spatiotemporal control of therapy. Additionally, significant biological hurdles impact clinical translation, including the formation of protein coronae, immune clearance, and heterogeneity within the tumor microenvironment (TME). Advanced targeting techniques, including passive, active, and subcellular targeting, enhance treatment specificity and efficacy. Integrating nanotechnology with biomaterials can achieve regenerative applications and deliver therapeutics, such as targeted drug delivery systems that improve treatment outcomes for various diseases. Developing technologies, such as artificial intelligence (AI) and 3D/4D printing, also open up new possibilities for precision medicine. However, issues with toxicity, scalability, and regulatory frameworks remain, which could make it harder for these new methods to be widely used in clinical settings.