Pharmacokinetics, tissue distribution and anti-tumor effect of low density lipoprotein peptide conjugated submicron emulsions

Docetaxel (Doc) is a potent chemotherapy for cancer but its application is limited by poor water solubility and high risk of side effects. To improve these issues, low density lipoprotein receptor (LDLR) targeted peptide-RLT (CEKLKEAFRLTRKRGLKLA) modified Docetaxel-loaded submicron emulsions (RLT-DocSEs) had been developed. Docetaxel-loaded SEs (DocSEs) and cationic DocSEs (DocCSEs) were also prepared for comparison. To evaluate the tumor-targeting ability and anti-tumor efficacy, DocSEs, DocCSEs, and RLT-DocSEs were administrated intravenously to rats respectively. The pharmacokinetic parameters of three formulations were significantly different. In vivo distribution study was conducted in mice and the results indicated that RLT-DocSEs possessed increased tumor targeting ability than DocSEs and DocCSEs. RLT-DocSEs also resulted in a higher tumor inhibition rate and a better anti-tumor efficacy in mice. All the results suggested that RLT-DocSEs could be a potential formulation for the injection of Doc with enhanced tumor targeting and anti-tumor efficacy.