Chapter 5 Herbal bioenhancers in cancer drug delivery

Effective chemotherapy with minimal adverse effects is the ultimate goal of cancer therapy. However, ever-mutating tumor cells, and difficult-to-target tumor environment impede the effective delivery of anticancer drugs to the tumor site. Additionally, suboptimal biopharmaceutical properties of anticancer drugs and drug-efflux transporters further make an increased therapeutic dose necessary to achieve the desired chemotherapeutic effect. The administration of higher doses of anticancer agents leads to several dose-dependent adverse effects, some of which could be more serious than the actual disease. Therefore, improving the therapeutic efficacy and reducing the dose of the anticancer drug is of paramount importance to improve the benefit vs. risk ratio of the cancer therapy. Bioenhancers are the agents that can improve the bioavailability and efficacy of the drugs upon concomitant administration. They can reduce the drug dose, cost of the therapy, drug resistance, and adverse effects. Plant-derived bioenhancers such as piperine, glycyrrhizin, quercetin, curcumin, allicin, cumin, and naringin have been explored for optimizing the therapeutic outcome of cancer chemotherapy. Bioenhancers have been shown to improve efficacy and reduce the dose of anticancer drugs by several mechanisms such as improvement of the pharmacokinetic profile of the cytotoxic agent via drug permeation enhancement across the physiological barriers, inhibition of the drug efflux transporters, and suppression or alteration of the drug metabolism, and elimination. Many of these agents have been shown to inherently possess some anticancer activity. Hence, several preclinical studies involving a combination of the bioenhancer with the anticancer agent have demonstrated synergism and improved pharmacodynamics. This chapter elucidates the mechanism of action and potential applications of various plant-based bioenhancers to augment outcomes of cancer chemotherapy.