A Comprehensive Review of Genistein and Chitosan: Mechanistic Foundations, Regulatory Roadmap, and Future Research Directions

INTRODUCTION: Genistein, a phytoestrogen with multi-target anticancer activity, and chitosan, a biocompatible polymer with versatile drug carrier properties, are increasingly investigated for use in advanced drug delivery systems. Cancer remains a leading cause of mortality globally, with current therapeutic approaches like systemic toxicity, non-specific drug delivery, multidrug resistance, and limited bioavailability of therapeutic compounds. METHODS: This review synthesized evidence from PubMed, Scopus, Web of Science, Science Direct, and Google Patents. Most of the studies involving genistein, chitosan, nano-formulations, pharmacokinetics, regulatory guidelines, and patents were screened. Some of the recent patents from 2020 to 2025 on drug delivery have been analyzed to map translation development. RESULTS: Moreover, the genistein chitosan systems are positioned as a synergistic co-therapy platform. Composite systems such as nanoparticles, liposomes, hydrogels, and micelles show significant improvements in bioavailability (5-10-fold), tumor retention, and reduced systemic toxicity in preclinical models. The clinical implications of this integrated system are profound. DISCUSSION: Despite strong preclinical data, regulatory challenges persist, including variability in the molecular weight of genistein and chitosan, limited nanotoxicology standards, and classification inconsistencies for natural products. The regulatory landscapes of the developing and non-developing countries, which evolved across key pharmaceutical jurisdictions including the FDA, EMA, CDSCO, PMDA, AND NMPA. CONCLUSION: Genistein and chitosan drug delivery systems represent a promising approach for precision oncology, offering improved pharmacokinetics, targeted delivery, and reduced toxicity. This review also critically addresses the regulatory gaps, biocompatibility, and modular delivery systems.