Advanced liposomal nanoplatforms for flavonoid delivery: a mechanistic and comparative perspective in hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is a common and life-threatening type of liver cancer, and its treatment results are frequently restricted by late diagnosis, drug resistance, systemic toxicity, and limited specificity of traditional treatment methods, including chemotherapy, surgery, and targeted therapy. Flavonoids, which are a family of naturally-occurring polyphenolic compounds, have been of significant interest in the past few years, based on their antioxidant and anti-inflammatory, anti-proliferative and pro-apoptotic characteristics. These compounds can control major signaling pathways related to tumor development and progression and are good candidates for the treatment of HCC. Poor aqueous solubility, high metabolism, and low bioavailability, however, greatly limit the clinical use of flavonoids. The delivery system of flavonoids based on liposomes is the possible solution to these restrictions as they preserve the stability, solubility, and tumor-targeting characteristics and protect the flavonoid against degradation, encasing it directly into a vesicle of phospholipid. The improvement of therapeutic performance has been implemented through various approaches to formulation, which are inclusive of thin-film hydration, PEGylation, ligand-mediated targeting, and stimuli-responsive systems. The review has provided the latest developments in liposomal delivery of flavonoids as a tool in the application of HCC which include formulation, physicochemical characterization, and therapeutic effects of flavonoids based on in vitro and in vivo experiments. It is also applied by giving a comparative study with conventional therapies. Moreover, such crucial issues about clinical translation as formulation stability, regulatory standards, expandability, and lack of clinical evidence are severely tackled. Lastly, the outlook of the future in the areas of targeted delivery, combination therapy, and clinical validation are described. In general, the liposomal delivery of flavonoids is a compelling approach to enhancing the therapeutic response of hepatocellular carcinoma.