The antitumor efficacy of docetaxel is enhanced by encapsulation in novel amphiphilic polymer cholesterol-coupled tocopheryl polyethylene glycol 1000 succinate micelles.

Tocopheryl polyethylene glycol 1000 succinate (TPGS) is considered a promising surfactant, but its high critical micelle concentration (CMC) limits its application. Cholesterol is hydrophobic, can act as a tumor-targeting ligand, and has strong binding ability with taxoids. Based on this information, we coupled cholesterol with TPGS to synthesize cholesterol-coupled TPGS (TPGS-CHMC), which had a lower CMC than pure TPGS. The TPGS-CHMC was used to prepare micelles loading with docetaxel (DTX) by a self-assembly method. DTX-loaded TPGS-CHMC micelles were globule-shaped, 13.3 ± 2.0 nm in size, and had a zeta potential of -4.66 ± 0.41 mv. In vitro release studies demonstrated the delayed release property of the micelles, which also had a relatively high encapsulation efficiency and drug loading content of 99.2 and 3.20%, respectively. Furthermore, the micelles were stable in vitro at a dilution of 100-fold. In vivo antitumor studies showed that the DTX-loaded TPGS-CHMC micelles significantly enhanced the antitumor activity of DTX in S180 tumor-bearing mice. Interestingly, the blank TPGS-CHMC micelles also showed antitumor activity. Our results demonstrate that TPGS-CHMC is a promising system for DTX delivery that may be suitable for other hydrophobic antitumor drugs.