title: Investigation of Hexadecylphosphocholine (miltefosine) usage in Pegylated liposomal doxorubicin as a synergistic ingredient: In vitro and in vivo evaluation in mice bearing C26 colon carcinoma and B16F0 melanoma.
abstract: In this investigation, Hexadecylphosphocholine (HePC, miltefosine) was being used as a new ingredient in Pegylated liposomal doxorubicin (PLD) and different aspects of this integration such as its effect on doxorubicin (Dox) release and cell uptake, cytotoxicity of liposomes, in vivo distribution and half-life clearance time of Dox as well as median survival time were illustrated. The liposomal formulations were Pegylated liposomal doxorubicin containing 0, 0.5, 1, 2 and 4% mole ratios of HePC (HePC-PLD) and their respective Dox-free liposomes (HePC-PLs). The cells used were colon carcinoma (C26), adriamycin-resistant breast cancer (MCF-7-ADR), and B16F0 melanoma cell lines, of which C26 and B16F0 cells were exploited for tumoring in BALB/c and C57Bl/6 mice, respectively. In most cases, increase in miltefosine percentage resulted in physically liposomal instability, increased Dox delivery and toxicity and reduced blood half-life of Dox. Overall, HePC 4% -PLD and PLD differed significantly in many respects and it was considered too toxic to be injected at the same dose (15mg Dox/ kg) as PLD. Although HePC 2% -PLD could extend the median survival time marginally in comparison to PLD, the concept of HePC- containing liposomes merits further investigation.
authors: Biotechnology Research Center, Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 91775-1365, Iran.
authors: Manouchehr
authors: M
authors: Teymouri
authors: Nanotechnology Research Center, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad 91775-1365, Iran.
authors: Hamidreza
authors: H
authors: Farzaneh
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: Nuclear Medicine Research Center, Mashhad University of Medical Sciences, Mashhad 91775-1365, Iran.
authors: Kayvan
authors: K
authors: Sadri
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 / Q000493:pharmacokinetics / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy*; D004317:Doxorubicin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D016503:Drug Delivery Systems; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005260:Female; D008545:Melanoma / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009368:Neoplasm Transplantation; D010767:Phosphorylcholine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; C506643:liposomal doxorubicin; D010767:Phosphorylcholine; D011092:Polyethylene Glycols; C039128:miltefosine; D004317:Doxorubicin
keywords: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (PubChem CID: 64965); Chemotherapy; Cholesterol (PubChem CID: 5997); Doxorubicin; Doxorubicin Hydrochloride (PubChem CID: 443939); Hexadecylphosphocholine; Miltefosine; Miltefosine (PubChem CID: 3599); Pegylated liposomes