Novel nanomicelles based on rebaudioside A: A potential nanoplatform for oral delivery of honokiol with enhanced oral bioavailability and antitumor activity

[Display omitted] Honokiol (HK) has a variety of biological activities, but its poor solubility limits its application. Rebaudioside A (RA) is able to self-assemble into micelles, which can be used for oral delivery of anticancer drugs. This study aims to create and evaluate a nano-sized anticancer drug delivery system based on RA, as RA micelles are thought to strengthen the therapeutic effects of HK. The results showed that RA and HK can be formulated into self-assembling micelles (RA-HK) with a size of 4.356 ± 0.142 nm and uniform distribution (PDI = 0.1906 ± 0.0184). Moreover, RA-HK could enhance the antitumor activity of HK in vitro. Further, it was shown that RA-HK can induce G0/G1 cycle arrest, apoptosis, and reactive oxygen species (ROS) generation in HuH-7 cells. The results for this mechanism indicate that RA-HK can induce DNA damage as well as changes in cycle and apoptotic-related proteins and activate the ERK signaling pathway. The in vivo antitumor results showed that RA-HK could also enhance the antitumor activity of HK in mice and does not induce any side effects. The pharmacokinetic results illustrate that RA-HK can increase the oral bioavailability of HK that and RA-HK is widely distributed in rats. Taken together, the above results prove that RA is a novel oral nano-drug delivery system with great potential for the delivery of hydrophobic antitumor drugs, such as HK.