title: Pharmacokinetics, tissue distribution and anti-tumor effect of low density lipoprotein peptide conjugated submicron emulsions.
abstract: 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.
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, HeNan 45001 PR China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: The First Affiliated Hospital, Zhengzhou University, Zhengzhou, HeNan 450052 PR China.
authors.forename: Jinhong
authors.initials: J
authors.lastname: Miao
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, HeNan 45001 PR China.
authors.forename: Pengchao
authors.initials: P
authors.lastname: Sun
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, HeNan 45001 PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liang
authors.affiliation: Academy of Medical and Pharmaceutical Sciences of Zhengzhou University, Zhengzhou, HeNan 450052 PR China.
authors.forename: Haiying
authors.initials: H
authors.lastname: Hua
authors.affiliation: The First Affiliated Hospital, Zhengzhou University, Zhengzhou, HeNan 450052 PR China.
authors.forename: Yusheng
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, HeNan 45001 PR China. Electronic address: zhaoyx@zzu.edu.cn.
authors.forename: Yongxing
authors.initials: Y
authors.lastname: Zhao
mesh_terms: D061605:Administration, Intravenous; D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D000077143:Docetaxel; D004655:Emulsions / Q000737:chemistry*; D008297:Male; D051379:Mice; D010316:Particle Size; D010455:Peptides / Q000737:chemistry*; D017207:Rats, Sprague-Dawley; D011973:Receptors, LDL / Q000737:chemistry*; D012509:Sarcoma / Q000188:drug therapy / Q000473:pathology; D055672:Static Electricity; D043823:Taxoids / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use; D014018:Tissue Distribution / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D004655:Emulsions; D010455:Peptides; D011973:Receptors, LDL; D043823:Taxoids; D000077143:Docetaxel
keywords: Docetaxel; Low density lipoprotein peptide; Pharmacokinetics; Submicron emulsions; Tumor targeting