Yana Gvozdeva, Pétia Georgieva, Plamen Katsarov
Imatinib (IMT) is a small-molecule tyrosine kinase inhibitor that primarily targets platelet-derived growth factor receptor-β and related kinases. Beyond its established efficacy in chronic myeloid leukemia, IMT has also demonstrated therapeutic benefits in gastrointestinal stromal tumors, dermatofibrosarcoma, acute lymphoblastic leukemia, and as a second-line treatment for aggressive systemic mastocytosis or as an anti-Mycobacterium agent. From a physicochemical perspective, IMT exhibits poor aqueous solubility but high membrane permeability, classifying it as a Biopharmaceutics Classification System Class II compound. Pharmacokinetically, IMT shows variable oral absorption and a prolonged terminal half-life, resulting in dose-dependent systemic exposure. Despite relatively high oral bioavailability, its clinical use requires large doses to achieve therapeutic efficacy, underscoring the need for advanced drug delivery strategies. Nano- and microscale delivery systems offer promising approaches to enhance tumor-specific accumulation through the enhanced permeability and retention effect while mitigating resistance mechanisms. However, achieving high drug loading introduces formulation challenges, such as controlling particle size distribution, polydispersity, and scalability. Moreover, designing carriers capable of controlled release without premature leakage remains crucial for maintaining systemic bioavailability and therapeutic performance. Emerging delivery platforms—including polymeric, lipid-based, carbon-derived, and stimuli-responsive nanocarriers—have shown significant potential in overcoming these limitations. Such systems can enhance IMT’s bioavailability, improve selective tumor targeting, and minimize systemic toxicity, thereby advancing its translational potential. This review aims to highlight the different biomedical applications of IMT and off-label uses, and to discuss current advances in drug delivery to optimize its clinical efficacy and safety profile.