title: pH-sensitive, polymer modified, plasma stable niosomes: promising carriers for anti-cancer drugs.
abstract: The aim of this study was the design and evaluation of a novel plasma stable, pH-sensitive niosomal formulation of Mitoxantrone by a modified ethanol injection method. Cholesterol hemisuccinate was added instead of cholesterol in order to produce pH-sensitivity property and using PEG-Poly (monomethyl itaconate)-CholC6 (PEG-PMMI-CholC6) copolymer introduced simultaneously pH-sensitivity and plasma stability properties in prepared niosomes. The pH-sensitivity and cytotoxicity of Mitoxantrone niosomes were evaluated in vitro in phosphate buffer with different pHs as well as using human ovarian cancer cell line (OVCAR-3), human breast cancer cell line (MCF-7) and human umbilical vein endothelial cells (HUVEC). Results showed that both cholesterol derivatives bearing formulations had pH-sensitive property and were found to release their contents under mild acidic conditions rapidly. In addition, the PEG-PMMI-CholC6-based niosomes could reserve the pH-sensitivity after incubation in plasma. Both Mitoxantrone-loaded pH-sensitive niosomes showed higher cytotoxicity than the conventional niosomes on OVCAR-3 and MCF-7 cell lines. However, both pH-sensitive niosomes exhibited lower cytotoxic effect on HUVEC cell line. Plasma stable, pH-sensitive niosomes could improve the cytotoxic effect and reduce the side effects of anti-tumor drugs.
authors.affiliation: Tabriz University of Medical Sciences, Tabriz, Iran, Research Center for Pharmaceutical Nanotechnology.
authors.forename: Dena
authors.initials: D
authors.lastname: Tila
authors.affiliation: Tabriz University of Medical Sciences, Tabriz, Iran, Research Center for Pharmaceutical Nanotechnology.
authors.forename: Seyede Narjes
authors.initials: SN
authors.lastname: Yazdani-Arazi
authors.affiliation: Tabriz University of Medical Sciences, Tabriz, Iran, 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.
authors.forename: Saeed
authors.initials: S
authors.lastname: Ghanbarzadeh
authors.affiliation: Tabriz University of Medical Sciences, Tabriz, Iran, Research Center for Pharmaceutical Nanotechnology ; Tabriz University of Medical Sciences, Tabriz, Iran, Student Research Committee, Faculty of Pharmacy.
authors.forename: Sanam
authors.initials: S
authors.lastname: Arami
authors.affiliation: Chemistry Department, Science Faculty, Azarbaijan Shahid Madani University,Tabriz, Iran.
authors.forename: Zhaleh
authors.initials: Z
authors.lastname: Pourmoazzen
keywords: Mitoxantrone; cytotoxic effect; pH-sensitive plasma stable niosome