title: The influence of phospholipid on the physicochemical properties and anti-tumor efficacy of liposomes encapsulating cisplatin in mice bearing C26 colon carcinoma.
abstract: SPI-077, cisplatin stealth liposome, is the best illustration of poor cisplatin release from liposomes and the subsequent negligible therapeutic activity. For this reason, optimizing drug release kinetics is desirable. In this report, cisplatin was encapsulated in liposomes composed of different phosphatidylcholines with various phase transition temperatures (Tm) (HSPC, DPPC, DMPC, soy phosphatidylcholine (SPC)), cholesterol and mPEG2000-DSPE. In vitro cytotoxicity studies indicated that lowering Tm of lipids increases cisplatin release; the highest cytotoxicity was observed in SPCs. Cisplatin plasma concentration was also sensitive to the transition temperature. The highest platinum concentration observed after treatment with HSPC and DPPC liposomes, whilst the lowest was observed with SPC. HSPC and DPPC containing liposomes showed the highest therapeutic efficacy and survival with DPPC exhibited better efficacy in mouse model of C26. It seems that DPPC with Tm (41.5°C) nearly, or close to body temperature maintains good drug retention in blood circulation. Upon extravasation through permeable tumor microvasculature, it gradually releases its payload in the tumor area better than HSPC, with a greater Tm of 55°C. Our data suggests, the choice of Tm for lipid mixture directed to a considerable extent the rate of cisplatin elimination from plasma and therapeutic effects.
authors: Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 91775-1365, Iran.
authors: Seyedeh Hoda
authors: SH
authors: Alavizadeh
authors: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 91775-1365, Iran.
authors: Ali
authors: A
authors: Badiee
authors: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 91775-1365, Iran.
authors: Shiva
authors: S
authors: Golmohammadzadeh
authors: Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 91775-1365, Iran. Electronic address: jafarimr@mums.ac.ir.
authors: Mahmoud Reza
authors: MR
authors: Jaafari
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002784:Cholesterol / Q000737:chemistry; D002945:Cisplatin / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D003106:Colon / Q000473:pathology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D008081:Liposomes; D008807:Mice, Inbred BALB C; D044367:Phase Transition; D010743:Phospholipids / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry; D047368:Tumor Burden / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D010743:Phospholipids; C422270:SPI-77, liposomal; D011092:Polyethylene Glycols; D002784:Cholesterol; D002945:Cisplatin
keywords: C26 colon carcinoma; Cancer treatment; Chloroform (PubChem CID: 6212); Cholesterol (PubChem CID: 5997); Cisplatin; Cisplatin (PubChem CID: 2767); Ethylenediaminetetraacetic acid (PubChem CID: 6049); Hydrochloric acid (PubChem CID: 313); Isopropanol (PubChem CID: 3776); Liposome; Methylphenazonium methosulfate (PubChem CID: 9285); Nitric acid (PubChem CID: 944); Phase transition temperature; Sodium chloride (PubChem CID: 5234); Triton X-100 (PubChem CID: 5590)