Targeted-nanoliposomal combretastatin A4 (CA-4) as an efficient antivascular candidate in the metastatic cancer treatment

A number of antiangiogenic drugs have been approved by the Food and Drug Administration which are used in cancer therapy, and variety of other agents in several stages of clinical development or in preclinical assessment. Among these, combretastatin A4 (CA-4) is an under-researched inhibitor of angiogenesis that shows potential activity in the treatment of advanced tumors with migration capacity. However, its clinical application has been limited due to poor water solubility, low bioavailability, rapid metabolism, and systemic elimination. During the last decade, numerous investigations have been done to overcome these problems by using different CA-4 delivery systems or developing produgs of CA-4 or its structural analogs. Nevertheless, these strategies could not be efficient out of the undesired side effects on normal tissues. Nanoliposomal CA-4 not only benefits from the advantage of using liposomal drugs as opposed to free drugs but also can accumulate in the tumor site via specific targeting ligands, which leads to efficient targeting and enhancement of bioavailability. To the best of our knowledge, we consider an important attempt to understand different factors that might influence the CA-4 loading and release pattern of liposomes and the consequent results in tumor therapy. In this review, we shed light on various studied liposomal CA-4 formulations showing application thereof in cancer treatment.