Drug induced self-assembly of triblock copolymers into polymersomes for the synergistic dual-drug delivery of platinum drugs and paclitaxel

Callari, M; Wong, S; Lu, H; Aldrich-Wright, J; de Souza, P; Stenzel, MH

Drug induced self-assembly of triblock copolymers into polymersomes for the synergistic dual-drug delivery of platinum drugs and paclitaxel

Callari, M Wong, S Lu, H

Aldrich-Wright, J de Souza, P Stenzel, MH

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Publisher:: Royal Society of Chemistry
Publication Type:: Journal Article
Citation:: Polymer Chemistry, 2017, 8, (40), pp. 6289-6299
Issue Date:: 2017

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Field	Value	Language
dc.contributor.author	Callari, M
dc.contributor.author	Wong, S
dc.contributor.author	Lu, H https://orcid.org/0000-0001-6932-1900
dc.contributor.author	Aldrich-Wright, J
dc.contributor.author	de Souza, P
dc.contributor.author	Stenzel, MH
dc.date.accessioned	2022-09-16T03:46:50Z
dc.date.available	2022-09-16T03:46:50Z
dc.date.issued	2017
dc.identifier.citation	Polymer Chemistry, 2017, 8, (40), pp. 6289-6299
dc.identifier.issn	1759-9954
dc.identifier.issn	1759-9962
dc.identifier.uri	http://hdl.handle.net/10453/161846
dc.description.abstract	Co-delivery of two drugs in one nanoparticle is increasingly used to overcome, for example, multi-drug resistance in cancer therapy and therefore suitable drug carriers need to be developed. In this work, a well-known polymer based on poly(glutamic acid) (PGA) and poly(ethylene glycol) (PEG), PGA-PEG-PGA, was employed as a reactive scaffold for the attachment of paclitaxel (Ptx) and platinum(iv) prodrugs. While the polymer itself is water-soluble, the chemical conjugation of both drugs induces self-assembly into polymersomes with a high drug loading content of 28 wt% of Ptx and 11 wt% of the platinum drug. These polymersomes were found to be stable against enzymatic degradation, yet allowed the release of the platinum drugs in a reductive environment. Twenty-two percent of platinum was released after 48 hours, suggesting a two-step model where Pt-drugs are released within a few days, while Ptx has a slower, prolonged, release. Using traditional A549 and LNCap cell lines in 2D culture to test cytotoxicity, the free Ptx drug performed better than Ptx delivered in nanoparticles, as expected, due to the slow cleavage of the drug. However, experiments in 3D cell culture models with A549 spheroids revealed that the drug carrier enabled a higher accumulation of Pt-drugs inside the cells, and after 14 days incubation, the drug-loaded carrier performed slightly better than the free drugs over the longer timeframe. Further, Chou-Talalay analysis confirmed the synergistic effect of the combination of platinum drug and Ptx in the nanoparticle system.
dc.language	English
dc.publisher	Royal Society of Chemistry
dc.relation.ispartof	Polymer Chemistry
dc.relation.isbasedon	10.1039/c7py01162h
dc.rights	info:eu-repo/semantics/closedAccess
dc.subject	0303 Macromolecular and Materials Chemistry, 0307 Theoretical and Computational Chemistry
dc.title	Drug induced self-assembly of triblock copolymers into polymersomes for the synergistic dual-drug delivery of platinum drugs and paclitaxel
dc.type	Journal Article
utslib.citation.volume	8
utslib.for	0303 Macromolecular and Materials Chemistry
utslib.for	0307 Theoretical and Computational Chemistry
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	*
pubs.consider-herdc	false
dc.date.updated	2022-09-16T03:46:49Z
pubs.issue	40
pubs.publication-status	Published
pubs.volume	8
utslib.citation.issue	40

Abstract:

Co-delivery of two drugs in one nanoparticle is increasingly used to overcome, for example, multi-drug resistance in cancer therapy and therefore suitable drug carriers need to be developed. In this work, a well-known polymer based on poly(glutamic acid) (PGA) and poly(ethylene glycol) (PEG), PGA-PEG-PGA, was employed as a reactive scaffold for the attachment of paclitaxel (Ptx) and platinum(iv) prodrugs. While the polymer itself is water-soluble, the chemical conjugation of both drugs induces self-assembly into polymersomes with a high drug loading content of 28 wt% of Ptx and 11 wt% of the platinum drug. These polymersomes were found to be stable against enzymatic degradation, yet allowed the release of the platinum drugs in a reductive environment. Twenty-two percent of platinum was released after 48 hours, suggesting a two-step model where Pt-drugs are released within a few days, while Ptx has a slower, prolonged, release. Using traditional A549 and LNCap cell lines in 2D culture to test cytotoxicity, the free Ptx drug performed better than Ptx delivered in nanoparticles, as expected, due to the slow cleavage of the drug. However, experiments in 3D cell culture models with A549 spheroids revealed that the drug carrier enabled a higher accumulation of Pt-drugs inside the cells, and after 14 days incubation, the drug-loaded carrier performed slightly better than the free drugs over the longer timeframe. Further, Chou-Talalay analysis confirmed the synergistic effect of the combination of platinum drug and Ptx in the nanoparticle system.

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http://hdl.handle.net/10453/161846