Explicit analysis of in vivo, meterological and statistical hurdles in successful clinical translation of targeted nanomedicines and plausible remedial strategies.

Introduction: The potential of nanomedicine in alleviating different disorders is immense, but its clinical translation rate is severely debilitated, despite promising preclinical study outcomes. For therapeutically successful targeted delivery of nanomedicines, it is crucial to understand why well-designed nanomedicines often fail during clinical trials.

Areas covered: This review comprehensively explores the multifactorial reasons behind the poor clinical success rate of nanomedicines, including pathophysiological complexity, limitations in statistical analysis, inadequate animal models, variability in the EPR effect, and manufacturing challenges. Special focus is placed on the misinterpretation and misuse of statistical tools in preclinical studies, which significantly reduces data interpretation and clinical predictability. The review is based on an in-depth literature survey of recent advances and failures in nanomedicine translation, with an emphasis on incorporating simulation models and synthesized data to overcome the challenges of statistics.

Expert opinion: Addressing translational gaps requires a multidisciplinary approach, refined preclinical models, robust statistical frameworks, and adaptive clinical designs that are essential. Innovative tools, such as CTGAN and personalized trial strategies, can bridge the preclinical-clinical divide. To realize the full potential of nanomedicine, it is crucial to resolve foundational issues in experimental design, data interpretation, analytical frameworks, and regulatory compliance.