Factors affecting drug delivery system translation: A focus on advanced technologies, biological barriers, and...

The clinical translation of DDS is still one of the most challenging issues for the further development of therapeutic breakthroughs, especially for cancer and complex diseases. This review provides a critical overview of the factors that influence the translation of DDS, highlighting biological and non-biological barriers that challenge their success. Additionally, their impacts are conceptually clarified in biological aspects, including immunity, biocompatibility and the tumor microenvironment, on the performance and site-selectivity of DDS. Secondly, the review discusses non-biological barriers, such as manufacturing scale-up aspects, the regulatory challenges in different markets (e.g., the U.S, EU, and China), and the necessity of early and ongoing regulatory interactions to enable acceptable approval strategies in the relevant authorities. Emerging technologies (such as organ-on-a-chip models and artificial intelligence (AI)) are highlighted as transformative tools that could revolutionize the accuracy of preclinical testing and of DDS design. Through dissecting current challenges and available alternatives, this review also presents perspectives to promote the development of DDS and their clinical translation, ensuring their practical use in therapeutics.