Advances in Organoids for Drug Development: From Discovery to Delivery

Abstract

Organoid technology has emerged as a promising platform for drug development by enabling the in vitro reconstruction of human tissue architecture, cellular heterogeneity, and key physiological functions. Compared with conventional two-dimensional cell cultures and animal models, organoids provide improved physiological relevance and translational potential. In this review, we systematically summarize the principles of organoid generation, including cell sources, construction strategies, and model classification, and discuss recent advances in integrating organoids with emerging technologies such as microfluidics, gene editing, artificial intelligence, and three-dimensional bioprinting. We further provide a comprehensive overview of organoid applications across the drug development pipeline, including target identification and drug discovery, pharmacodynamic evaluation, absorption, distribution, metabolism, and excretion (ADME) studies, and multi-organ toxicity assessment. Particular emphasis is placed on their expanding role in evaluating advanced drug delivery systems, including transdermal, pulmonary, and nanomedicine-based intelligent delivery platforms, where organoids enable systematic investigation of delivery–penetration–distribution–efficacy–toxicity processes under physiologically relevant conditions. In addition, current challenges, including model standardization, tissue maturation, vascularization, immune integration, and in vitro–in vivo extrapolation, are critically discussed together with future perspectives. Overall, organoid technology is evolving from an emerging experimental model into an integrated platform for drug discovery and translational research, providing new opportunities for more predictive, efficient, and personalized drug development.