Percutaneous penetration of anticancer agents: Past, present and future

Cancer occurs as a result of alterations in oncogenes, tumor-suppressor genes, and microRNA genes. Over the past few decades, efforts have been made to understand the dominant oncogenes and tumor suppressor genes whose respective activation/upregulation or loss of function serve to impart aberrant properties on normal cells. Cancer continues to be a source of public health concern due to widespread prevalence, morbidity and mortality. The most common types include but are not limited to lung, prostate, colorectal, breast, ovarian and skin cancers. In 2012, there were more than 8 million deaths worldwide related to cancer from 14 million new cases. Cancer chemotherapy frequently requires long periods of multiple intravenous infusions which may compel patients to abandon treatment. One approach to overcome this challenge is through the use of transdermal drug delivery systems. The major obstacle with transdermal drug delivery is that the stratum corneum, which is the outermost layer of the skin, hinders the penetration of therapeutic agents. An avalanche of techniques is available to enhance the penetration of anticancer agents across the skin including iontophoresis, sonophoresis, microneedles, prodrugs, microemulsions and elastic liposomes. In this review, attention is focused on the numerous techniques used to overcome the skin barrier and enhance the percutaneous penetration of anticancer agents.