Advances in New Approach Methodologies for Assessing ADME Properties of Nano-formulations

Conventional animal models face ethical concerns and scientific limitations, as interspecies differences often fail to capture the unique pharmacokinetics of nanomaterials.This review highlights advances in Non-Animal Models, including organoid-based systems that replicate human tissue structure, microfluidic organ-on-chip platforms that mimic dynamic physiology, and computational approaches such as physiologically based pharmacokinetic (PBPK) modelling, molecular dynamics, and machine learning.Innovations such as vascularized organoids, multi-organ chip networks, and artificial intelligence-driven refinement are evaluated for their potential to improve predictive accuracy.Remaining challenges, including scalability, standardisation, and incorporation of immune and microbiome components, are critically discussed.By integrating technological advances with regulatory perspectives, this review underscores New Approach Methodologies as a transformative pathway toward more ethical, human-relevant, and predictive nanomedicine development.