title: Combination of hybrid peptide with biodegradable gelatin hydrogel for controlled release and enhancement of anti-tumor activity in vivo.
abstract: We previously reported that the EGFR2R-lytic hybrid peptide has cytotoxic and anti-tumor activities both in vitro and in vivo. In this study, to improve the peptide pharmacokinetics and its anti-tumor activity after intravenous injection, we prepared biodegradable gelatin hydrogel nanoparticles as the delivery system of peptide. The complex is formed through the electrostatic interaction between the cationic peptide and anionic gelatin. In vitro release studies confirmed that the peptide was released from the complex in phosphate-buffered saline (PBS) solution containing fetal bovine serum at 37°C within 48h, whereas little release was observed in PBS solution. In vivo release studies indicated that the anti-tumor activity of the complex was more effective than that of peptide treatment alone, and high tumor accumulation of the peptide was observed in the mice treated with the complex. Furthermore, the plasma area under the concentration curve (AUC) and half-life (T1/2) values of the complex were higher than those of the peptide treatment alone, respectively. These results demonstrate that the rate of peptide release was controlled by the gelatin, and that the complex had a longer circulation time and enhanced its anti-tumor activity in vivo.
authors.affiliation: Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan.
authors.forename: Arong
authors.initials: A
authors.lastname: Gaowa
authors.affiliation: Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan.
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Horibe
authors.affiliation: Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kohno
authors.affiliation: Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sato
authors.affiliation: Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Harada
authors.affiliation: Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hiraoka
authors.affiliation: Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Tabata
authors.affiliation: Department of Pharmacoepidemiology, Graduate School of Medicine and Public Health, Kyoto University, Kyoto, Japan. Electronic address: kawakami.koji.4e@kyoto-u.ac.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Kawakami
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D003692:Delayed-Action Preparations / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005780:Gelatin / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D057809:HEK293 Cells; D006801:Humans; D020100:Hydrogels; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000188:drug therapy / Q000473:pathology; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use; D047368:Tumor Burden / Q000187:drug effects; D023041:Xenograft Model Antitumor Assays
chemical_list: D000970:Antineoplastic Agents; D003692:Delayed-Action Preparations; C586251:EGFR-lytic peptide; D020100:Hydrogels; D011993:Recombinant Fusion Proteins; D005780:Gelatin
keywords: Anti-tumor activity; Controlled release; DDS; Gelatin hydrogel; Hybrid peptide; Pharmacokinetics