Nanoformulation of dual bexarotene-tailed high drug loading phospholipid conjugate with

Bexarotene (Bex), a synthetic retinoid X receptor-selective activator, has been proved to be an efficacious chemotherapeutic agent. But, its clinical application is limited due to the poor solubility. In this report, dual bexarotenetailed phospholipid (DBTP) conjugate based nanovesides were prepared in order to develop new nanoformulation. DBTP conjugate was first synthesized by conjugating two Bex molecules with glycerophosphorylcholine (GPC) through facial esterification. The amphiphilic DBTP nanovesicles were prepared without any additive by reverse-phase evaporation method. They were characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). The results revealed that the DBTP nanovesicles have a spherical structure with an average diameter approximately 138.7 nm and a negatively charged surface (-33.3 +/- 2.5 mV). The loading efficiency of Bex is 76 wt% after a simple calculation. In vitro degradation of DBTP nanovesicles and the release of Bex were further studied in detail. The results demonstrated that DBTP nanovesides were stable in neutral environment but degraded in a weakly acidic condition and released parent drug Bex effectively. Cellular uptake was investigated by confocal laser scanning microscope (CISM) and liquid chromatography-mass spectroscopy (LC-MS). The results demonstrated the successful internalization and intracellular release of DBTP nanovesicles. Furthermore, the cytotoxicity analysis and apoptosis of the nanovesicles showed higher antitumor activities compared with free Bex. In a conclusion, DBTP nanovesides could be an effective nanoformulation of Bex. (C) 2017 Elsevier B.V. All rights reserved.