Sorafenib—Drug Delivery Strategies in Primary Liver Cancer

Current primary liver cancer therapies, including sorafenib and transarterial chemoembolization, face significant limitations due to chemoresistance caused by impaired drug uptake, altered metabolism, and other genetic modulations. These challenges contribute to relapse rates of 50–80% within five years. The need for improved treatment strategies (adjuvant therapy, unsatisfactory enhanced permeability and retention (EPR) effect) has driven research into advanced drug delivery systems, including targeted nanoparticles, biomaterials, and combinatory approaches. Therefore, this review evaluates recent advancements in primary liver cancer pharmacotherapy, focusing on the potential of drug delivery systems for sorafenib and its derivatives. Approaches such as leveraging Kupffer cells for tumor migration or utilizing smaller NPs for inter-/intracellular delivery, address EPR limitations. Biomaterials and targeted therapies focusing on targeting have demonstrated effectiveness in increasing tumor-specific delivery, but clinical evidence remains limited. Combination therapies have emerged as an interesting solution to overcoming chemoresistance or to broadening therapeutic functionality. Biomimetic delivery systems, employing blood cells or exosomes, provide methods for targeting tumors, preventing metastasis, and strengthening immune responses. However, significant differences between preclinical models and human physiology remain a barrier to translating these findings into clinical success. Future research must focus on the development of adjuvant therapy and refining drug delivery systems to overcome the limitations of tumor heterogeneity and low drug accumulation.