NANOTECHNOLOGY-BASED DRUG DELIVERY SYSTEMS: A SYSTEMATIC REVIEW OF ADVANCES, THERAPEUTIC APPLICATIONS, AND BARRIERS TO CLINICAL TRANSLATION

Background: Nanotechnology has emerged as one of the most transformative platforms in modern pharmaceutics, offering solutions to longstanding problems of poor aqueous solubility, non-specific biodistribution, rapid clearance, and off-target toxicity associated with conventional drug therapy. Objective: This systematic review synthesizes the peer-reviewed literature on nanotechnology-based drug delivery systems (NDDS), with emphasis on lipid-based carriers (liposomes, solid lipid nanoparticles, and lipid nanoparticles), polymeric carriers (PLGA nanoparticles and polymeric micelles), and dendrimers, and evaluates the mechanisms, targeting strategies, safety considerations, and regulatory barriers that determine their clinical translatability. Methods: A structured literature search was conducted across PubMed/MEDLINE, Scopus, Web of Science, and Google Scholar for records published primarily between 2012 and 2026, using combinations of the terms "nanoparticle," "drug delivery," "liposome," "PLGA," "solid lipid nanoparticle," "dendrimer," "lipid nanoparticle," "blood-brain barrier," "nanotoxicology," and "clinical translation." Results: Fifty primary and secondary sources meeting the eligibility criteria were included. The evidence indicates that nanocarriers consistently improve pharmacokinetic profiles and enable tumor- or tissue-selective accumulation through passive (enhanced permeability and retention) and active (ligand-mediated) targeting, and that lipid nanoparticles have achieved landmark clinical success as mRNA vaccine and siRNA carriers. However, translational barriers persist, including inconsistent physicochemical characterization, scale-up and batch-to-batch reproducibility problems, unresolved long-term toxicity profiles, and an incompletely harmonized global regulatory framework. Conclusion: Nanotechnology-based drug delivery continues to mature from a promising laboratory concept into a validated clinical modality, but continued progress will depend on standardized characterization protocols, mechanistic toxicology studies, and internationally harmonized regulatory guidance.