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

Sevimli, S; Inci, F; Zareie, HM; Bulmus, V

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

Sevimli, S Inci, F Zareie, HM Bulmus, V

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Publication Type:: Journal Article
Citation:: Biomacromolecules, 2012, 13 (10), pp. 3064 - 3075
Issue Date:: 2012-10-08

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Field	Value	Language
dc.contributor.author	Sevimli, S	en_US
dc.contributor.author	Inci, F	en_US
dc.contributor.author	Zareie, HM	en_US
dc.contributor.author	Bulmus, V	en_US
dc.date.issued	2012-10-08	en_US
dc.identifier.citation	Biomacromolecules, 2012, 13 (10), pp. 3064 - 3075	en_US
dc.identifier.issn	1525-7797	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. © 2012 American Chemical Society.	en_US
dc.relation.ispartof	Biomacromolecules	en_US
dc.relation.isbasedon	10.1021/bm300846e	en_US
dc.subject.classification	Polymers	en_US
dc.subject.mesh	Cell Line, Tumor	en_US
dc.subject.mesh	Cell Membrane	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Polymethacrylic Acids	en_US
dc.subject.mesh	Cholesterol	en_US
dc.subject.mesh	Cholesterol Esters	en_US
dc.subject.mesh	Lipid Bilayers	en_US
dc.subject.mesh	Drug Delivery Systems	en_US
dc.subject.mesh	Cell Survival	en_US
dc.subject.mesh	Hydrogen-Ion Concentration	en_US
dc.title	Well-defined cholesterol polymers with pH-controlled membrane switching activity	en_US
dc.type	Journal Article
utslib.citation.volume	10	en_US
utslib.citation.volume	13	en_US
utslib.for	0303 Macromolecular and Materials Chemistry	en_US
utslib.for	03 Chemical Sciences	en_US
utslib.for	06 Biological Sciences	en_US
utslib.for	09 Engineering	en_US
pubs.embargo.period	Not known	en_US
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 Mathematical and Physical Sciences
utslib.copyright.status	closed_access
pubs.issue	10	en_US
pubs.publication-status	Published	en_US
pubs.volume	13	en_US

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. © 2012 American Chemical Society.

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