title: Therapeutic Efficacy of Cisplatin Thermosensitive Liposomes upon Mild Hyperthermia in C26 Tumor Bearing BALB/c Mice.
abstract: This study reports on the activity of thermosensitive liposomes (TSLs) incorporating different HSPC ratios in DPPC/MSPC/PEG2000-DSPE matrix (90/10/4) plus mild hyperthermia (HT) (42 °C). TSLs were loaded with a poorly membrane permeable anticancer drug, cisplatin, through the passive equilibration method. The addition of HSPC to the corresponding DPPC lipid matrix increased the transition temperature. In vitro data demonstrated >90% cisplatin leakage from nanosized DPPC 90-lyso-TSL (LTSL) within 10 min at 42 °C, while other TSLs bearing HSPC showed greater stability. The plasma kinetics of cisplatin demonstrated higher cisplatin leakage from DPPC 90-LTSL in the first 4 h (from 17.4 to 0.4 μg/mL) compared to other formulations. Indeed, increasing HSPC fraction in liposome bilayers significantly improved drug retention in blood. Though DPPC 90-LTSL plus one-step HT was expected to provide a unique drug release, the premature drug leakage as well as the likely wash-back of a great portion of drug into the blood circulation resulted in reduced survival. On the other hand, stabilized DPPC 30/HSPC 60/MSPC 10/PEG2000-DSPE 4 liposomes plus two-step HT greatly enhanced the survival of animals. In particular, the improved delivery of cisplatin through stabilized DPPC 30/HSPC 60/MSPC 10/PEG2000-DSPE 4 liposomes in two-step mild HT enhanced antitumor efficacy compared to other formulations. Thus, prolonged exposure of cancer cells to cisplatin through stabilized liposomes would be an efficient approach in improving the survival of animals.
authors.affiliation: Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences , Mashhad 91775-1365, Iran.
authors.forename: Seyedeh Hoda
authors.initials: SH
authors.lastname: Alavizadeh
authors.affiliation: Department of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences , Tehran, Iran.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Gheybi
authors.affiliation: Immunogenetic and Cell Culture Department, Immunology Research Center, School of Medicine, Mashhad University of Medical Sciences , Mashhad, Iran.
authors.forename: Amin Reza
authors.initials: AR
authors.lastname: Nikpoor
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences , Mashhad, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Badiee
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences , Mashhad, Iran.
authors.forename: Shiva
authors.initials: S
authors.lastname: Golmohammadzadeh
authors.affiliation: Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences , Mashhad 91775-1365, Iran.
authors.forename: Mahmoud Reza
authors.identifier: 0000-0003-3908-6828
authors.initials: MR
authors.lastname: Jaafari
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D005260:Female; D008081:Liposomes / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D009369:Neoplasms / Q000188:drug therapy*; D010714:Phosphatidylethanolamines / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D044366:Transition Temperature
chemical_list: C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D000970:Antineoplastic Agents; D008081:Liposomes; D010714:Phosphatidylethanolamines; D011092:Polyethylene Glycols; D002945:Cisplatin
keywords: cancer; cisplatin; hyperthermia; thermosensitive liposomes; triggered release