New PTX-HS15/T80 Mixed Micelles: Cytotoxicity, Pharmacokinetics and Tissue Distribution.

Abstract

Compared with single micelle, the new PTX-HS15/T80 mixed micelle system (PTX-HS15/T80 MMs) had achieved better results in solubilization, stability, and sensitization before. Therefore, we intend to further verify the potential advantages of the mixed micelle delivery system through in vitro cytotoxicity test and animal test to understand the anticancer effect and in vivo pharmaceutical behavior of the system. In vitro cytotoxicity test showed that the new PTX-HS15/T80 MMs had a stronger ability to inhibit the proliferation of cancer cells. The results of in vivo pharmacokinetics showed that the micelle had shorter half-life, higher clearance rate, and lower blood concentration and had good blood clearance characteristics. The results of in vivo tissue distribution showed that, compared with the single micelle Taxol®, the new PTX-HS15/T80 MMs had good distribution characteristics in the lung (AUC (lung 0-4H) increased about 26%) and low concentration in the heart (AUC (Heart 0-4H) decreased about 10%). Paclitaxel was mainly metabolized through the liver and kidney. The above results suggested that the new PTX-HS15/T80 MMs may have a certain therapeutic potential against lung cancer and reduce the toxic and side effects. In general, the mixed micelle delivery system was not only simple and cheap to prepare but also had certain advantages in vitro and in vivo, indicating that the combination of surfactants provides a good choice for solving the problem of insoluble drug delivery.