Selecting nanocarrier platforms for drug delivery: a criteria-based, translational review integrating CQA/CMC and immune interactions

Nanotechnology and nanomedicine have transformative potential for the development of drug delivery systems. By enabling more effective and safer delivery of active agents to target tissues, they can increase bioavailability, reduce adverse effects, and provide opportunities for targeted therapy. However, the clinical success of nanocarriers depends not only on their nanoscale characteristic but also on the concurrent optimization of critical quality and product development parameters (CQA/CMC), including particle size and size distribution, surface charge and chemistry, loading efficiency, release profile, stability in biological environments, scalable manufacturing, sterilization, shelf life, and batch-to-batch consistency. This review comparatively examines different platforms—primarily liposomes, micelles, solid lipid nanoparticles (SLN/NLC), polymeric nanoparticles, dendrimers, carbon-based nanostructures (particularly carbon nanotubes), and metallic/metal-oxide nanoparticles—in terms of cargo type (hydrophobic/hydrophilic/biomolecules), targeting strategies, release mechanisms, and routes of administration (intravenous, oral, inhalational, topical/transdermal, and barrier crossing), and discusses the major advantages and limitations of each platform. In particular, although nanocarriers may enhance efficacy while contributing to the preservation of healthy tissues in complex diseases such as cancer, hemocompatibility, protein corona effects, complement activation/CARPA risk, and uncertainties regarding long-term biotransformation and toxicity are critical factors that may constrain clinical translation. Overall, the study emphasizes that, rather than seeking a single superior nanocarrier, a criteria-based selection approach aligned with indication, route of administration, and product development requirements is more likely to strengthen research design and increase the probability of successful clinical transition. In addition to design and targeting principles, we emphasize clinically relevant constraints including immune interactions (e.g., protein corona and complement activation) and manufacturing considerations such as critical quality attributes, reproducibility, and scalability. Finally, we propose a criteria-based selection perspective to support choosing an appropriate nanocarrier platform based on indication, administration route, and cargo properties.