Abstract: The aim of this study was to investigate the feasibility of using polyethylene glycol(PEG)distearate as liquid crystalline(LC)materials to prepare drug-loaded LC nanoparticles(LCNPs).Two LC materials,mPEG distearate(mPEG350-DS)and PEG distearate(S-PEG400-S),were respectively synthesized.Both obtained derivatives could form lyotropic LC in water,and the LC of S-PEG400-S could be stably dispersed to prepare LCNPs.With docetaxel as the model drug,the LCNPs with good drug-loading capacity were obtained by adding appropriate amount of lecithin into the formula.The particle size,ζ potential,encapsulation efficiency,loading capacity,and content of the docetaxel-loaded LCNPs were 137.9 nm,-19.7 mV,96.5%,3.4%,and 98.2%of the labeled amount(namely 2 mg/mL),respectively.The docetaxel-loaded LCNPs showed better antitumor effects and remarkably longer blood circulation time than the commercially available injection(Taxotere?)in in vitro antitumor experiment and in vivo pharmacokinetic study.The LC phase in the LCNPs was inferred to be sponge(L3)phase according to the observations of polarizing microscopy,small angle X-ray scattering and cryo-transmission electron microscopy.In conclusion,the S-PEG400-S showed a good prospect for LCNPs-based drug delivery system.