NANOPARTICLE SYNTHESIS FOR TARGETED DRUG DELIVERY: A REVIEW OF DESIGN STRATEGIES, FABRICATION METHODS, AND TRANSLATIONAL CHALLENGES

Abstract

Nanoparticle (NP)-based drug delivery has emerged as one of the most active frontiers in pharmaceutical and materials chemistry, offering the ability to protect labile drugs, improve solubility, and direct therapeutic payloads to diseased tissue while sparing healthy organs. This review synthesizes current literature on the synthesis, functionalization, and targeting performance of nanoparticle carriers, with emphasis on organic systems (liposomes, polymeric nanoparticles, lipid nanoparticles), inorganic systems (gold, iron oxide, and mesoporous silica nanoparticles), and hybrid architectures. Bottom-up fabrication approaches, including nanoprecipitation, thin-film hydration, high-pressure homogenization, and microfluidic self-assembly, are compared against traditional top-down methods, with microfluidic mixing highlighted as the dominant strategy for achieving reproducible size distribution and encapsulation efficiency at scale. Targeting mechanisms are examined across two axes: passive accumulation via the enhanced permeability and retention (EPR) effect and active, ligand-mediated recognition of overexpressed receptors on target cells, alongside stimuli-responsive systems that release payloads in response to pH, redox potential, enzymatic activity, or external fields. The review then evaluates persistent barriers to clinical translation, including batch-to-batch variability, incomplete understanding of the protein corona, long-term toxicity of inorganic cores, and regulatory ambiguity surrounding nanomedicine characterization. Recent advances (2023–2025) in gold-nanoparticle chemotherapy conjugates, mesoporous silica stimuli-responsive carriers, and acoustically driven microfluidic liposome production are discussed as evidence of the field's rapid technical maturation. The review concludes that continued progress depends on standardizing characterization protocols, integrating artificial-intelligence-assisted formulation design, and strengthening interdisciplinary collaboration between chemists, pharmacologists, and regulators to close the translational gap between bench-scale synthesis and clinical deployment.