A translational framework to DELIVER nanomedicines to the clinic

• Published in: Nature nanotechnology Vol. 19; no. 11; pp. 1597 - 1611
• Main Authors: Joyce, Paul, Allen, Christine J., Alonso, María José, Ashford, Marianne, Bradbury, Michelle S., Germain, Matthieu, Kavallaris, Maria, Langer, Robert, Lammers, Twan, Peracchia, Maria Teresa, Popat, Amirali, Prestidge, Clive A., Rijcken, Cristianne J. F., Sarmento, Bruno, Schmid, Ruth B., Schroeder, Avi, Subramaniam, Santhni, Thorn, Chelsea R., Whitehead, Kathryn A., Zhao, Chun-Xia, Santos, Hélder A.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.11.2024; Nature Publishing Group
• Subjects: 631/61/350/354; 631/61/54/152; 639/925/352/152; 639/925/357/354; Animals; Biocompatibility; Biomarkers; Chemistry and Materials Science; Clinical outcomes; Clinical trials; Clinical Trials as Topic; Design; Developmental stages; Disease; Drug Delivery Systems - methods; Drug dosages; FDA approval; Funding; Humans; Jurisdiction; Manufacturing; Materials Science; Nanomaterials; Nanomedicine - methods; Nanostructures - administration & dosage; Nanostructures - adverse effects; Nanotechnology; Nanotechnology and Microengineering; Pharmaceuticals; Physicochemical properties; Registration; Regulatory approval; Reproducibility; Review Article; Risk reduction; Standard of care; Success; Toxicity; Translation; Translational Research, Biomedical - methods; Vaccines
• ISSN: 1748-3387; 1748-3395; 1748-3395
• DOI: 10.1038/s41565-024-01754-7

Nanomedicines have created a paradigm shift in healthcare. Yet fundamental barriers still exist that prevent or delay the clinical translation of nanomedicines. Critical hurdles inhibiting clinical success include poor understanding of nanomedicines’ physicochemical properties, limited exposure in the cell or tissue of interest, poor reproducibility of preclinical outcomes in clinical trials, and biocompatibility concerns. Barriers that delay translation include industrial scale-up or scale-down and good manufacturing practices, funding and navigating the regulatory environment. Here we propose the DELIVER framework comprising the core principles to be realized during preclinical development to promote clinical investigation of nanomedicines. The proposed framework comes with design, experimental, manufacturing, preclinical, clinical, regulatory and business considerations, which we recommend investigators to carefully review during early-stage nanomedicine design and development to mitigate risk and enable timely clinical success. By reducing development time and clinical trial failure, it is envisaged that this framework will help accelerate the clinical translation and maximize the impact of nanomedicines. The authors propose a framework to be followed during preclinical investigation of nanomedicines to increase their translatability potential.