title: Tat peptide and hexadecylphosphocholine introduction into pegylated liposomal doxorubicin: An in vitro and in vivo study on drug cellular delivery, release, biodistribution and antitumor activity.
abstract: We have investigated the co-addition of hexadecylphosphocholine (HePC) and a Tat derived peptide (Tat), coupled to Maleimide-PEG2000-DSPE pegylated liposomal doxorubicin (PLD) in many respects, including drug and liposome cellular delivery, drug release, biodistribution, in vivo cell delivery and antitumor activity. The liposomes were HePC-free and -containing liposomes, from which liposomes with 25, 50, 100 and 200 numbers of Tat/liposome were prepared. Similarly, DiI-C18 (3)-model liposomes (DiI-L and DiI-HePC-L) were prepared. HePC and Tat increased cellular delivery of Dox and cytotoxicity in B16F0 melanoma and C26 colon carcinoma cells. Tat enhanced liposome-cell interaction and caused Dox burst release. HePC and Tat reduced the serum retention time of liposomal Dox, slightly and dramatically, respectively. In comparison, Tat-liposomes enhanced Dox delivery to liver and spleen cells 3h post-injection. Likewise, Dox content of these tissues and tumor was lower at 24h. The naïve liposomes retarded tumor growth more effectively and their related median survival time of the treated C26 bearing BALB/c mice was longer than those of Tat-liposomes (MST>45days versus MST<38days). Overall liposomes exhibiting sustained drug release and negligible cell interaction were more suitable delivery systems in targeting cancerous tumors and suppressing their growth.
authors.affiliation: Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, 91775-1365, Iran.
authors.forename: Manouchehr
authors.initials: M
authors.lastname: Teymouri
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, 91775-1365, Iran.
authors.forename: Ali
authors.initials: A
authors.lastname: Badiee
authors.affiliation: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, 91775-1365, Iran.
authors.forename: Shiva
authors.initials: S
authors.lastname: Golmohammadzadeh
authors.affiliation: Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad, 91775-1365, Iran.
authors.forename: Kayvan
authors.initials: K
authors.lastname: Sadri
authors.affiliation: Department of Physiology and Pharmacology, Immunogenetics Research Center, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari 48471-91971, Iran.
authors.forename: Javad
authors.initials: J
authors.lastname: Akhtari
authors.affiliation: Nanobiotechnology Research Centre, Baqiyatallah University of Medical Sciences, Tehran, Iran.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Mellat
authors.affiliation: Immunogenetic and Cell Culture Department, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
authors.forename: Amin Reza
authors.initials: AR
authors.lastname: Nikpoor
authors.affiliation: 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.forename: Mahmoud Reza
authors.initials: MR
authors.lastname: Jaafari
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D005260:Female; D008081:Liposomes; D051379:Mice; D008807:Mice, Inbred BALB C; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000378:metabolism; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000378:metabolism; D014018:Tissue Distribution / Q000187:drug effects / Q000502:physiology; D023041:Xenograft Model Antitumor Assays / Q000379:methods; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000008:administration & dosage* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D010446:Peptide Fragments; C506643:liposomal doxorubicin; D054322:tat Gene Products, Human Immunodeficiency Virus; C490722:tat peptide (49-57), Human immunodeficiency virus 1; D010767:Phosphorylcholine; D011092:Polyethylene Glycols; C039128:miltefosine; D004317:Doxorubicin
keywords: Biodistribution; Doxorubicin; Hexadecylphosphocholine; Liposome cell delivery; Tat-derived peptide