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 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
utslib.copyright.status Closed Access
utslib.copyright.date 2015-04-15 12:17:09.805752+10
pubs.consider-herdc true
utslib.collection.history School of Physics and Advanced Materials (ID: 343)
utslib.collection.history Closed (ID: 3)


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