title: Plasma stable, pH-sensitive fusogenic polymer-modified liposomes: A promising carrier for mitoxantrone.
abstract: pH-sensitive liposomes are designed to undergo acid-triggered destabilization. In the present study, we prepared polymer-modified, plasma stable, pH-sensitive fusogenic mitoxantrone liposomes to increase efficacy and selectivity on cancer cell lines. Conventional liposomes were prepared using cholesterol and dipalmitoyl-sn-glycero-3-phosphatidylethanolamine. Dioleoylphosphatidylethanolamine and a cholesteryl derivative, poly(monomethylitaconate)-co-poly(N,N-dimethylaminoethyl methacrylate) (PMMI-co-PDMAEMA), were used for the preparation of pH-sensitive fusogenic liposomes. Using polyethylene glycol (PEG)-poly(monomethylitaconate)-CholC6 (PEG-PMMI-CholC6) copolymers instead of cholesterol introduced pH-sensitive and plasma stability properties simultaneously in prepared liposomes. All formulations were prepared by thin film hydration method and subsequently, pH-sensitivity and stability in human serum were evaluated. The ability of pH-sensitive fusogenic liposomes to enhance the mitoxantrone cytotoxicity and selectivity in cancerous cell lines was assessed in vitro compared to normal cell line using human breast cancer cell line (MCF-7), human prostate cancer cell line (PC-3), and human umbilical vein endothelial cells line. Results revealed that both PMMI-co-PDMAEMA and PEG-PMMI-CholC6-based formulations showed pH-sensitive property and were found to rapidly release mitoxantrone under mildly acidic conditions. Nevertheless, only the PEG-PMMI-CholC6-based liposomes preserved pH-sensitivity after incubation in plasma. Mitoxantrone loaded-pH-sensitive fusogenic liposomes exhibited a higher cytotoxicity than the control conventional liposomes on MCF-7 and PC-3 cell lines. On the contrary, both pH-sensitive fusogenic liposomes showed lower cytotoxic effect on human umbilical vein endothelial cell line. Plasma stable, pH-sensitive fusogenic liposomes are promising carriers for enhancing the efficiency and selectivity, besides reduction of the side effects of anticancer agents.
authors: Research Center for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran Student Research Committee, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors: Saeed
authors: S
authors: Ghanbarzadeh
authors: Student Research Committee, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran Pharmaceutical Biotechnology Department, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors: Sanam
authors: S
authors: Arami
authors: Chemistry Department, Science Faculty, Azarbaijan Shahid Madani University, Tabriz, Iran.
authors: Zhaleh
authors: Z
authors: Pourmoazzen
authors: Department of Pharmaceutics, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran Department of Pharmacognosy, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran.
authors: Javad
authors: J
authors: Ghasemian-Yadegari
authors: Student Research Committee, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran Khorramia@tbzmed.ac.ir.
authors: Arash
authors: A
authors: Khorrami
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001672:Biocompatible Materials / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004337:Drug Carriers / Q000737:chemistry; D004355:Drug Stability; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008081:Liposomes / Q000737:chemistry; D061986:MCF-7 Cells; D008422:Materials Testing; D008561:Membrane Fusion; D008689:Methacrylates / Q000737:chemistry; D008942:Mitoxantrone / Q000008:administration & dosage* / Q000009:adverse effects; D009369:Neoplasms / Q000188:drug therapy* / Q000473:pathology; D009757:Nylons / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry
chemical_list: D000970:Antineoplastic Agents; D001672:Biocompatible Materials; D004337:Drug Carriers; D008081:Liposomes; D008689:Methacrylates; D009757:Nylons; D011108:Polymers; C407037:poly(2-(dimethylamino)ethyl methacrylate); D011092:Polyethylene Glycols; D008942:Mitoxantrone
keywords: Plasma stable; mitoxantrone; pH-sensitive fusogenic liposomes