Swollen Micelles for the Preparation of Gated, Squeezable, pH-Responsive Drug Carriers

Qu, J-B; Chapman, R; Chen, F; Lu, H; Stenzel, MH

Swollen Micelles for the Preparation of Gated, Squeezable, pH-Responsive Drug Carriers

Qu, J-B Chapman, R Chen, F Lu, H

Stenzel, MH

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Publisher:: AMER CHEMICAL SOC
Publication Type:: Journal Article
Citation:: ACS Applied Materials & Interfaces, 2017, 9, (16), pp. 13865-13874
Issue Date:: 2017

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Field	Value	Language
dc.contributor.author	Qu, J-B
dc.contributor.author	Chapman, R
dc.contributor.author	Chen, F
dc.contributor.author	Lu, H https://orcid.org/0000-0001-6932-1900
dc.contributor.author	Stenzel, MH
dc.date.accessioned	2022-10-03T20:52:39Z
dc.date.available	2022-10-03T20:52:39Z
dc.date.issued	2017
dc.identifier.citation	ACS Applied Materials & Interfaces, 2017, 9, (16), pp. 13865-13874
dc.identifier.issn	1944-8244
dc.identifier.issn	1944-8252
dc.identifier.uri	http://hdl.handle.net/10453/162247
dc.description.abstract	Natural variations in pH levels of tissues in the body make it an attractive stimuli to trigger drug release from a delivery vehicle. A number of such carriers have been developed but achieving high drug loading combined with low leakage at physiological pH and tunable controlled release at the site of action is an ongoing challenge. Here we report a novel strategy for the synthesis of entirely hydrophilic stimuli-responsive nanocarriers with high passive loading efficiency of doxorubicin (DOX), which show good stability at pH 7 and rapid tunable drug release at intracellular pH. The particles (Dh = 120-150 nm), are prepared by cross-linking the core of swollen micelles of the triblock copolymer poly[poly(ethylene glycol) methyl ether methacrylate-b-N,N'-di(methylamino)ethyl methacrylate-b-tert-butyl methacrylate] (poly(PEGMEM A)-b- PDMAEMA-b-PtBMA)). After subsequent deprotection of the tert-butyl groups a hydrophilic poly(methacrylic acid) (PMAA) core is revealed. Due to the negative charge in the acidic core the particles absorb 100% of the DOX from solution at pH 7 at up to 50 wt % DOX/polymer, making them extremely simple to load. Unlike other systems, the DMAEMA "gating" shell ensures low drug leakage at pH 7, whereas physical shrinkage of the MAA core allows rapid release below pH 6. The particles deliver DOX with high efficiency to human pancreatic cancer AsPC-1 cell lines, even lowering the IC50 of DOX. As the particles are stable as a dry powder and can be loaded with any mixture of positively charged drugs without complex synthetic or purification steps, we propose they will find use in a range of delivery applications.
dc.format	Print-Electronic
dc.language	eng
dc.publisher	AMER CHEMICAL SOC
dc.relation.ispartof	ACS Applied Materials & Interfaces
dc.relation.isbasedon	10.1021/acsami.7b01120
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	03 Chemical Sciences, 09 Engineering
dc.subject.classification	Nanoscience & Nanotechnology
dc.subject.mesh	Doxorubicin
dc.subject.mesh	Drug Carriers
dc.subject.mesh	Drug Delivery Systems
dc.subject.mesh	Humans
dc.subject.mesh	Hydrogen-Ion Concentration
dc.subject.mesh	Micelles
dc.subject.mesh	Polyethylene Glycols
dc.subject.mesh	Polymers
dc.subject.mesh	Humans
dc.subject.mesh	Polyethylene Glycols
dc.subject.mesh	Doxorubicin
dc.subject.mesh	Polymers
dc.subject.mesh	Drug Carriers
dc.subject.mesh	Drug Delivery Systems
dc.subject.mesh	Micelles
dc.subject.mesh	Hydrogen-Ion Concentration
dc.title	Swollen Micelles for the Preparation of Gated, Squeezable, pH-Responsive Drug Carriers
dc.type	Journal Article
utslib.citation.volume	9
utslib.location.activity	United States
utslib.for	03 Chemical Sciences
utslib.for	09 Engineering
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology/School of Biomedical Engineering
pubs.organisational-group	/University of Technology Sydney/Strength - IBMD - Initiative for Biomedical Devices
utslib.copyright.status	closed_access	*
dc.date.updated	2022-10-03T20:52:35Z
pubs.issue	16
pubs.publication-status	Published
pubs.volume	9
utslib.citation.issue	16

Abstract:

Natural variations in pH levels of tissues in the body make it an attractive stimuli to trigger drug release from a delivery vehicle. A number of such carriers have been developed but achieving high drug loading combined with low leakage at physiological pH and tunable controlled release at the site of action is an ongoing challenge. Here we report a novel strategy for the synthesis of entirely hydrophilic stimuli-responsive nanocarriers with high passive loading efficiency of doxorubicin (DOX), which show good stability at pH 7 and rapid tunable drug release at intracellular pH. The particles (Dh = 120-150 nm), are prepared by cross-linking the core of swollen micelles of the triblock copolymer poly[poly(ethylene glycol) methyl ether methacrylate-b-N,N'-di(methylamino)ethyl methacrylate-b-tert-butyl methacrylate] (poly(PEGMEM A)-b- PDMAEMA-b-PtBMA)). After subsequent deprotection of the tert-butyl groups a hydrophilic poly(methacrylic acid) (PMAA) core is revealed. Due to the negative charge in the acidic core the particles absorb 100% of the DOX from solution at pH 7 at up to 50 wt % DOX/polymer, making them extremely simple to load. Unlike other systems, the DMAEMA "gating" shell ensures low drug leakage at pH 7, whereas physical shrinkage of the MAA core allows rapid release below pH 6. The particles deliver DOX with high efficiency to human pancreatic cancer AsPC-1 cell lines, even lowering the IC50 of DOX. As the particles are stable as a dry powder and can be loaded with any mixture of positively charged drugs without complex synthetic or purification steps, we propose they will find use in a range of delivery applications.

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http://hdl.handle.net/10453/162247