Oral administration of natural polyphenol-loaded natural polysaccharide-cloaked lipidic nanocarriers to improve efficacy against small-cell lung cancer.

Abstract Oral administration shows good tolerance in patients. Botanic anticancer drugs without serious side effects have attracted increased attention worldwide. However, oral delivery of natural anticancer drugs faces great challenges due to low solubility, gastrointestinal side effects, first-pass effects, and P-glycoprotein efflux. Here, we loaded the natural polyphenol curcumin (Cc) into natural polysaccharide-cloaked lipidic nanocarriers (Cc@CLNs) to improve the efficacy in small-cell lung cancer (SCLC) associated with oral administration. Compared to other nanoformulations, Cc@CLNs have advantages of simple operation, easy scale-up, low cost, and high safety. Cc@CLNs improve bioavailability by inducing synergistic effects (efficient cell membrane penetration, inherent muco-adhesiveness, resistance to pepsin and trypsin degradation, promoted dissolution, enhanced epithelia/M cellular uptake and inhibition of efflux transporters) and countering the tendency of nanocarriers to aggregate and fuse, which limit lipid-based nanosystems. In this study, we first evaluated the oral bioavailability of Cc@CLNs in rats and their efficacy in H446 tumor-bearing mice. The oral bioavailability increased by 8.94-fold, and the tumor growth inhibition rate doubled compared to that achieved with free Cc. We investigated the action of Cc against SCLC stem cells, and Cc@CLNs greatly enhanced this action. The expression of CD133 and ABCG2 in the Cc@CLNs group decreased by 38.05% and 32.57%, respectively, compared to the respective expression levels in the control.