Despite significant research progress in substantiating the therapeutic merits of nanomedicines and the emergence of sophisticated nanotechnologies, the translation of this knowledge into new therapeutic modalities has been sluggish, indicating the need for a more comprehensive understanding of how the unique physicochemical properties of nanoparticles affect their clinical applications. Particle size is a critical quality attribute that impacts the bio-fate of nanoparticles, yet precise knowledge of its effect remains elusive with discrepancies among literature reports. This review aims to address this scientific knowledge gap from a drug development perspective by highlighting potential inadequacies during the evaluation of particle size effects. We begin with a discussion on the major issues in particle size characterization along with the corresponding remedies. The influence of confounding factors on biological effects of particle size, including colloidal stability, polydispersity, and in vitro drug release, are addressed for establishing stronger in vitro-in vivo correlation. Particle size design and tailoring approaches for successful nanoparticulate drug delivery beyond parenteral administration are also illustrated. We believe a holistic understanding of the effect of particle size on bio-fate, combined with consistent nanoparticle manufacturing platforms and tailored characterization techniques, would expedite the translation of nanomedicines into clinical practice.
Keywords: In vitro/in vivo (IVIVC) correlation(s); Nanomedicine; Particle size; Pharmacokinetics; Site-specific delivery.
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