Research Information System
Journal of Drug Delivery Science and Technology, vol.115, 2026 (SCI-Expanded, Scopus)
Nanoparticle-based drug delivery systems are classified as non-biological complex drugs, where bioequivalence assessment remains challenging due to the lack of harmonized guidelines. For nab-paclitaxel, conventional manufacturing involves toxic solvents and high-shear processes, limiting scalability and reproducibility. Regulatory authorities require nanosimilarity demonstration: the FDA mandates in vivo pharmacokinetic comparisons and particle size similarity, while the EMA draft guideline allows a biowaiver if critical quality attributes such as drug-to-albumin ratio, particle size, amorphous content, and morphology match the reference. This study introduces a potentially scalable microfluidic approach to produce paclitaxel-loaded human serum albumin nanoparticles, eliminating toxic solvents and minimizing contamination. The method ensures controlled mixing through Dean vortex–assisted advection and was tested at bench-scale flow rates with scalability potential.Using a Quality by Design strategy, the formulation was optimized to achieve nanosimilar properties. The resulting nanoparticles showed physicochemical similarity to Abraxane®, confirmed by functional group, crystallinity, morphology, and secondary structure analyses, with consistent particle size distribution (d50 ≈ 142 nm, SPAN ≈1.5). In vitro release demonstrated similarity (f2 = 60 ± 3.22), and the drug-to-albumin ratio aligned with the reference. Anticancer studies in two- and three-dimensional 4T1 breast cancer models revealed no significant differences in activity compared to Abraxane® (p > 0.05). These findings indicate that the microfluidic-produced formulation possesses the critical attributes required for nanosimilarity and offers may offer potential to support regulatory approval pathways under current EMA and FDA frameworks. This innovative technology is supported by a national patent application (TR 2025/006435), further emphasizing its translational and industrial significance.