Technological approaches to tamoxifen nanoformulation: emphasis on modified chitosan-based nanoparticles: a review

Abstract

Tamoxifen remains a cornerstone in the treatment of estrogen receptor-positive breast cancer, yet its clinical performance is limited by poor aqueous solubility, high lipophilicity, and interindividual variability associated with CYP2D6-mediated formation of its more potent active metabolites. These challenges necessitate the development of advanced drug delivery systems. Nanotechnology-based formulations, particularly polymeric nanocarriers, have shown potential to improve solubility, pharmacokinetics, and therapeutic efficacy, although they do not inherently overcome CYP2D6-dependent metabolic variability. This review focuses on chitosan and its chemically modified derivatives as promising nanocarriers for tamoxifen delivery. Various modification strategies, including hydrophobic conjugation, graft copolymerization, and surface functionalization, are discussed in relation to encapsulation efficiency, release behavior, and biological performance. Reported studies demonstrate enhanced drug loading, sustained release, improved cellular uptake, and increased anticancer activity. Despite these advances, current research remains limited and lacks systematic comparisons. Further studies are required to optimize formulation design and support clinical translation of chitosan-based systems for tamoxifen therapy.