Navigating translational research in nanomedicine: A strategic guide to formulation and manufacturing.

Over the past two decades, extensive research has focused on both the fundamental and applied aspects of nanomedicine, driven by the compelling advantages that nanoparticles offer over their bulk counterparts. Despite this intensive research effort, fewer than 100 nanomedicines have been approved by the U.S. Food and Drug Administration and the European Medicines Agency since 1989. This disparity highlights a substantial gap in translational research, reflecting the disconnect between the prolific research in nanomedicine and the limited number of products that successfully reach and sustain themselves in the market. For instance, the nanomedicine DepoCyt, which received FDA approval in 1999 for the treatment of lymphomatous meningitis, was discontinued in 2017 due to persistent manufacturing issues. To address similar translational challenges, this review aims to identify and analyse issues related to the formulation design and manufacturing of nanomedicines. It provides an overview of the most prevalent manufacturing technologies and excipients used in nanomedicine production, followed by a critical evaluation of their clinical translatability. Furthermore, the review presents strategies for the rational formulation design and optimization of nanomedicine manufacturing, adhering to the principles of quality-by-design and quality risk management.