Phospholipid-hitchhiked Paclitaxel Nanoprodrugs for Tumor Treatment

Carriers play crucial roles in improving the drug delivery efficacy and antitumor activity. Here, two kinds of phospholipid-based carriers, including PEGylated phosphatidyl ethanolamine DSPE-PEG and phosphatidyl choline DPPC, were leveraged to encapsulate dimeric paclitaxel prodrugs to obtain the formulations. The impact of phospholipid-based carriers on the colloidal stability, cytotoxicity, bio-distribution and antitumor efficacy was systemically investigated. Compared with DPPC, DSPE-PEG could form uniform nanoformulations (DeP NPs). The average particle size and zeta-potential of DeP NPs were determined to be 201.1 nm and - 13.8 mV, respectively, by dynamic light scattering (DLS). The transmission electron microscopy (TEM) images confirmed their well-defined nanostructures. DeP NPs could remain stable in solutions containing 5% glucose, 10% FBS, and RPMI-1640 without serum. The hydrophobic interaction dominates the assembly of DSPE-PEG with PTX prodrug. Upon treated with 10 mmol/L H2O2, DeP NPs exhibited the oxidative responsive PTX release. DeP NPs could effectively be internalized by tumor cells, and exhibited more potent cytotoxicity towards cancer cells compared with normal cells. Furthermore, DeP NPs possessed good accumulation of drug at tumor sites and desirable antitumor performance. Our work provides valuable insight into the construction of phospholipid-based carriers material to deliver hydrophobic drugs. [GRAPHICS] .