Probiotic-derived microcarriers enhance the oral bioavailability of poorly absorbed anticancer drugs

Most anticancer drugs exhibit low absorption rates in the intestines; therefore, Intravenous (IV) administration is employed, which increases the risk of side effects. In this study, we demonstrated the effectiveness of a novel delivery system, the Probiotic-derived Microcarrier (PM), which improves the oral absorption rate of poorly absorbed pharmaceutical drugs, including doxorubicin and paclitaxel. In a concentration of 1x10¹² CFU of PM, doxorubicin accumulated to 3,512.6 μg, while paclitaxel reached 37.4 μg. When mice were administered PM-doxorubicin, the serum levels of doxorubicin significantly increased compared to those in mice that received doxorubicin alone. The enhanced bioavailability of doxorubicin was corroborated by the apparent anticancer effects of PM-doxorubicin observed in a mouse model. While orally administered doxorubicin did not exhibit antitumor efficacy, PM-doxorubicin demonstrated antitumor effects comparable to those of IV administration. The delivery of doxorubicin into the bloodstream via PM was facilitated by resident macrophages in the intestine, as evidenced by the observed interactions between PM and intestinal macrophages, as well as studies involving CSF-deficient mice. Our experimental findings indicate that the PM system can serve as an effective drug delivery vehicle, maximizing bioavailability through oral administration for drugs that are challenging to deliver orally, such as doxorubicin and paclitaxel.