Development and biomedical use of clay-based nanoparticulate systems: Recent advances and future directions

• Clay minerals possess layered/tubular architectures for controlled agent release. • Crystal structure/composition influence cation exchange capacity and plasticity. • Clays need purification to remove unwanted phases and enrich the clay fraction. • Agent loading is mediated by cation exchange, ion–dipole interactions and grafting. • Clinical translation is limited by variability, safety, and regulatory challenges. Clay-based nanoparticulate systems represent a promising class of materials for biomedical applications owing to their distinctive structural attributes, physicochemical properties, and intrinsic biocompatibility. This review provides an overview of recent advances in the preparation and biomedical utilization of clay nanoparticles, with particular emphasis on montmorillonite, halloysite, kaolinite, and illite. Special attention is devoted to the mechanisms and strategies for therapeutic agent loading, as well as the release pathways that enable sustained and controllable pharmacological activity. The discussion further addresses the biological interactions and functional roles of clay-based nanoparticles within diverse medical contexts. Despite their considerable potential, significant challenges to clinical translation persist, including issues related to toxicity, material reproducibility, and regulatory acceptance. To overcome these barriers, prospective strategies are delineated, encompassing the development of synthetic analogues, rigorous toxicological evaluation, and strengthened interdisciplinary collaboration, thereby informing future research directions.