Emerging Drug Delivery Strategies in Natural Product and Traditional Chinese Medicine Research: From Individual Approaches to Integrated Design

Natural products and bioactive constituents derived from traditional Chinese medicine are major sources of innovation in modern drug discovery and formulation, because of their remarkable structural diversity and multidimensional pharmacological activities. However, their clinical translation is frequently hindered by poor solubility, limited stability, low systemic exposure, inefficient tissue delivery, and narrow therapeutic windows. In recent years, drug delivery technologies have advanced the field beyond conventional solubilization, stabilization, and encapsulation toward more integrated strategies that enable targeted delivery, barrier penetration, microenvironment-responsive release, and combination therapy. More importantly, certain natural products are no longer regarded solely as therapeutic cargoes but are increasingly repurposed as functional excipients that enhance structural assembly, delivery efficiency, targeting, and pharmacological synergy. This shift is driving a transition from formulation optimization centered on single active ingredients to integrated drug–excipient design. It also enables contemporary delivery science to reconnect with the holistic philosophy of traditional Chinese medicine and the compatibility principles embodied in the monarch, minister, assistant, and guide framework. In this review, we examine the dual roles of natural products in drug delivery systems. We first summarize the developability barriers, delivery mechanisms, and representative optimization strategies associated with their application as therapeutic agents. We then highlight their emerging functions as excipients, focusing on key functional roles, construction paradigms, and recent advances in multifunctional delivery platforms integrating lipid nanoparticles, proteins, antibodies, nucleic acids, and living therapeutics. We further outline representative preclinical applications in cancer, neurodegenerative, metabolic, inflammatory, and immune-related diseases. Collectively, research on natural product-based delivery system is evolving from single-formulation optimization toward integrated design guided by disease context, material functionality, and the holistic principles of traditional Chinese medicine, thereby providing new conceptual and technological foundations for formulation innovation and clinical translation. Graphical Abstract: https://links.lww.com/AHM/A232