Well-defined cholesterol polymers with pH-controlled membrane switching activity.

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dc.contributor.author Sevimli, S
dc.contributor.author Inci, F
dc.contributor.author Zareie, HM
dc.contributor.author Bulmus, V
dc.date.accessioned 2014-04-03T01:22:27Z
dc.date.issued 2012-10
dc.identifier.citation Biomacromolecules, 2012, 13 (10), pp. 3064 - 3075
dc.identifier.issn 1525-7797
dc.identifier.other C1 en_US
dc.identifier.uri http://hdl.handle.net/10453/22787
dc.description.abstract Cholesterol has been used as an effective component of therapeutic delivery systems because of its ability to cross cellular membranes. Considering this, well-defined copolymers of methacrylic acid and cholesteryl methacrylate, poly(methacrylic acid-co-cholesteryl methacrylate) P(MAA-co-CMA), were generated as potential delivery system components for pH-controlled intracellular delivery of therapeutics. Statistical copolymers with varying cholesterol contents (2, 4, and 8 mol %) were synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. Dynamic light scattering (DLS) analysis showed that the hydrodynamic diameters of the copolymers in aqueous solutions ranged from 5 ± 0.3 to 7 ± 0.4 nm for the copolymers having 2 and 4 mol % CMA and 8 ± 1.1 to 13 ± 1.9 nm for the copolymer having 8 mol % CMA with increasing pH (pH 4.5-7.4). Atomic force microscopy (AFM) analysis revealed that the copolymer having 8 mol % CMA formed supramolecular assemblies while the copolymers having 2 and 4 mol % CMA existed as unimers in aqueous solution. The pH-responsive behavior of the copolymers was investigated via UV-visible spectroscopy revealing phase transitions at pH 3.9 for 2 mol % CMA, pH 4.7 for 4 mol % CMA, and pH 5.4 for 8 mol % CMA. Lipid bilayers and liposomes as models for cellular membranes were generated to probe their interactions with the synthesized copolymers. The interactions were determined in a pH-dependent manner (at pH 5.0 and 7.4) using surface plasmon resonance (SPR) spectroscopy and liposome leakage assay. Both the SPR analyses and liposome leakage assays indicated that the copolymer containing 2 mol % CMA displayed the greatest polymer-lipid interactions at pH 5.0, presenting the highest binding ability to the lipid bilayer surfaces, and also demonstrating the highest membrane destabilization activity. CellTiter-Blue assay showed that the copolymers did not affect the cell viability up to 30 μM over a period of 72 h.
dc.format Print-Electronic
dc.language eng
dc.relation.isbasedon 10.1021/bm300846e
dc.title Well-defined cholesterol polymers with pH-controlled membrane switching activity.
dc.type Journal Article
dc.parent Biomacromolecules
dc.journal.volume 10
dc.journal.volume 13
dc.journal.number 10 en_US
dc.publocation Washington en_US
dc.publocation United Kingdom
dc.identifier.startpage 3064 en_US
dc.identifier.endpage 3075 en_US
dc.cauo.name SCI.Faculty of Science en_US
dc.conference Verified OK en_US
dc.for 0303 Macromolecular and Materials Chemistry
dc.personcode 030414
dc.percentage 100 en_US
dc.classification.name Macromolecular and Materials Chemistry en_US
dc.classification.type FOR-08 en_US
dc.edition en_US
dc.edition 1
dc.custom en_US
dc.date.activity en_US
dc.location.activity en_US
dc.description.keywords INTRACELLULAR DRUG-DELIVERY; GENE DELIVERY; POLY(METHACRYLIC ACID); SIRNA DELIVERY; BLOCK-COPOLYMERS; AQUEOUS-SOLUTION; PHOSPHOLIPID-VESICLES; BUTYL METHACRYLATE; POLYION COMPLEX; STAR POLYMERS en_US
dc.description.keywords Cell Line, Tumor
dc.description.keywords Cell Line, Tumor
dc.description.keywords Cell Membrane
dc.description.keywords Cell Membrane
dc.description.keywords Humans
dc.description.keywords Humans
dc.description.keywords Polymethacrylic Acids
dc.description.keywords Polymethacrylic Acids
dc.description.keywords Cholesterol
dc.description.keywords Cholesterol
dc.description.keywords Cholesterol Esters
dc.description.keywords Cholesterol Esters
dc.description.keywords Lipid Bilayers
dc.description.keywords Lipid Bilayers
dc.description.keywords Drug Delivery Systems
dc.description.keywords Drug Delivery Systems
dc.description.keywords Cell Survival
dc.description.keywords Cell Survival
dc.description.keywords Hydrogen-Ion Concentration
dc.description.keywords Hydrogen-Ion Concentration
dc.description.keywords Cell Line, Tumor
dc.description.keywords Cell Membrane
dc.description.keywords Humans
dc.description.keywords Polymethacrylic Acids
dc.description.keywords Cholesterol
dc.description.keywords Cholesterol Esters
dc.description.keywords Lipid Bilayers
dc.description.keywords Drug Delivery Systems
dc.description.keywords Cell Survival
dc.description.keywords Hydrogen-Ion Concentration
dc.description.keywords Humans
dc.description.keywords Cell Membrane
dc.description.keywords Polymethacrylic Acids
dc.description.keywords Cholesterol
dc.description.keywords Cholesterol Esters
dc.description.keywords Lipid Bilayers
dc.description.keywords Drug Delivery Systems
dc.description.keywords Cell Survival
dc.description.keywords Cell Line, Tumor
dc.description.keywords Hydrogen-Ion Concentration
dc.description.keywords Humans
dc.description.keywords Cell Membrane
dc.description.keywords Polymethacrylic Acids
dc.description.keywords Cholesterol
dc.description.keywords Cholesterol Esters
dc.description.keywords Lipid Bilayers
dc.description.keywords Drug Delivery Systems
dc.description.keywords Cell Survival
dc.description.keywords Cell Line, Tumor
dc.description.keywords Hydrogen-Ion Concentration
pubs.embargo.period Not known
pubs.organisational-group /University of Technology Sydney
pubs.organisational-group /University of Technology Sydney/Faculty of Science
pubs.organisational-group /University of Technology Sydney/Faculty of Science/School of Physics and Advanced Materials


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