PEG-conjugated triacontanol micelles as docetaxel delivery systems for enhanced anti-cancer efficacy.

Abstract

PEGylated triacontanol (mPEG2k-b-TRIA) was developed as a dual-functional polymer with remarkable biocompatibility. The polymer could self-assemble to micelles with critical micelle concentration (CMC) 17.62μgmL-1. Docetaxel-loaded mPEG2k-b-TRIA micelles (DTX PMs) were fabricated to evaluate the feasibility of mPEG2k-b-TRIA as drug delivery system. DTX PMs achieved desirable particle size of 93.7nm, drug loading of 6.66%, and drug encapsulation efficiency of 89.87%. The drug release was based on first-order kinetics model, thus enabling prolonged release. Meanwhile, pharmacokinetic study also revealed that DTX PMs could improve the exposure level of DTX and prolong its systemic circulation time. Furthermore, DTX PMs demonstrated significantly enhanced cytotoxicity and cellular uptake in vitro compared with DTX solution. The in vivo tumor inhibition study carried out on MCF-7 bearing BALB/c mice model also validated that DTX PMs exhibited stronger anti-tumor activity but low toxicity. Notably, mPEG2k-b-TRIA made some contribution to inhibit the growth of breast cancer cells in vitro and in vivo, indicating the potential as anti-tumor complementary agents. All the results suggested that mPEG2k-b-TRIA polymer as a vehicle in the formulation of anti-cancer drugs may provide an effective way to improve their therapeutic efficacy. Consequently, the mPEG2k-b-TRIA polymers would be another promising carrier for hydrophobic anti-cancer drugs delivery.