title: Pharmacokinetics of peptide mediated delivery of anticancer drug ellipticine.
abstract: The amino acid pairing peptide EAK16-II (EAK) has shown the ability to stabilize the hydrophobic anticancer agent ellipticine (EPT) in aqueous solution. In this study, we investigate pharmacokinetics of the formulation of EAK-EPT complexes in vivo. The developed formulation can achieve a sufficiently high drug concentration required in vivo animal models. The nanostructure and surface properties of EAK-EPT complexes or nanoparticle were characterized by transmission electron microscopy (TEM) and zeta potential measurements, respectively. 12 healthy male SD rats were divided into EPT group and EAK-EPT group randomly. Rats in EPT group were tail intravenously injected with the EPT (20 mg/kg); rats in EAK-EPT group were injected with EAK-EPT complexes (EPT's concentration is 20 mg/kg). EPT was extracted from rat plasma with dexamethasone sodium phosphate as internal standards (IS). The pharmacokinetic parameters were obtained using high pressure liquid chromatography (HPLC). Significant differences in main pharmacokinetic parameters between EPT and EAK-EPT complexes were observed, demonstrating that the complexation with EAK prolongs the residence time of the drug and enlarges the area under the concentration-time curve (AUC). This means that EAK can serve as a suitable carrier to increase the bioavailability of EPT.
authors.affiliation: Department of Pharmacy, No. 3 People's Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People's Republic of China.
authors.forename: Weina
authors.initials: W
authors.lastname: Ma
authors.forename: Sheng
authors.initials: S
authors.lastname: Lu
authors.forename: Pei
authors.initials: P
authors.lastname: Pan
authors.forename: Parisa
authors.initials: P
authors.lastname: Sadatmousavi
authors.forename: Yongfang
authors.initials: Y
authors.lastname: Yuan
authors.forename: P
authors.initials: P
authors.lastname: Chen
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000970:Antineoplastic Agents / Q000493:pharmacokinetics*; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D004611:Ellipticines / Q000493:pharmacokinetics*; D008297:Male; D008958:Models, Molecular; D008969:Molecular Sequence Data; D049329:Nanostructures / Q000737:chemistry; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*; D011487:Protein Conformation; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D004611:Ellipticines; D010455:Peptides; C034192:ellipticine