Shear induced carboplatin binding within the cavity of a phospholipid mimic for increased anticancer efficacy

Vesicles 107 ± 19 nm in diameter, based on the self-assembly of tetra-para-phosphonomethyl calix[4]-arene bearing n-hexyl moieties attached to the phenolic oxygen centres, are effective in binding carboplatin within the cavity of the macrocycle under shear induced within a dynamic thin film in a con...

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Main Authors: Mo, J., Eggers, P., Chen, X., Ahamed, M., Becker, Thomas, Lim, L., Raston, C.
Format: Journal Article
Published: Nature Publishing Group 2015
Online Access:http://hdl.handle.net/20.500.11937/43632
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author Mo, J.
Eggers, P.
Chen, X.
Ahamed, M.
Becker, Thomas
Lim, L.
Raston, C.
author_facet Mo, J.
Eggers, P.
Chen, X.
Ahamed, M.
Becker, Thomas
Lim, L.
Raston, C.
author_sort Mo, J.
building Curtin Institutional Repository
collection Online Access
description Vesicles 107 ± 19 nm in diameter, based on the self-assembly of tetra-para-phosphonomethyl calix[4]-arene bearing n-hexyl moieties attached to the phenolic oxygen centres, are effective in binding carboplatin within the cavity of the macrocycle under shear induced within a dynamic thin film in a continuous flow vortex fluidic device. Post shearing the vesicles maintain similar diameters and retain carboplatin within the cavity of the calixarene in a hierarchical structure, with their size and morphology investigated using DLS, TEM, SEM and AFM. Location of the carboplatin was confirmed using NMR, FTIR, ESI-MS and EFTEM, with molecular modelling favouring the polar groups of carboplatin hydrogen bonded to phosphonic acid moieties and the four member cyclobutane ring directed into the cavity of the calixarene. The loading efficiency and release profile of carboplatin was investigated using LC-TOF/MS, with the high loading of the drug achieved under shear and preferential released at pH 5.5, offering scope for anti-cancer drug delivery. The hierarchical structured vesicles increase the efficacy of carboplatin by 4.5 fold on ovarian cancer cells, lowered the IC<inf>50</inf> concentration by 10 fold, and markedly increased the percent of cells in the S-phase (DNA replication) of the cell cycle.
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spelling curtin-20.500.11937-436322017-09-13T13:39:38Z Shear induced carboplatin binding within the cavity of a phospholipid mimic for increased anticancer efficacy Mo, J. Eggers, P. Chen, X. Ahamed, M. Becker, Thomas Lim, L. Raston, C. Vesicles 107 ± 19 nm in diameter, based on the self-assembly of tetra-para-phosphonomethyl calix[4]-arene bearing n-hexyl moieties attached to the phenolic oxygen centres, are effective in binding carboplatin within the cavity of the macrocycle under shear induced within a dynamic thin film in a continuous flow vortex fluidic device. Post shearing the vesicles maintain similar diameters and retain carboplatin within the cavity of the calixarene in a hierarchical structure, with their size and morphology investigated using DLS, TEM, SEM and AFM. Location of the carboplatin was confirmed using NMR, FTIR, ESI-MS and EFTEM, with molecular modelling favouring the polar groups of carboplatin hydrogen bonded to phosphonic acid moieties and the four member cyclobutane ring directed into the cavity of the calixarene. The loading efficiency and release profile of carboplatin was investigated using LC-TOF/MS, with the high loading of the drug achieved under shear and preferential released at pH 5.5, offering scope for anti-cancer drug delivery. The hierarchical structured vesicles increase the efficacy of carboplatin by 4.5 fold on ovarian cancer cells, lowered the IC<inf>50</inf> concentration by 10 fold, and markedly increased the percent of cells in the S-phase (DNA replication) of the cell cycle. 2015 Journal Article http://hdl.handle.net/20.500.11937/43632 10.1038/srep10414 Nature Publishing Group fulltext
spellingShingle Mo, J.
Eggers, P.
Chen, X.
Ahamed, M.
Becker, Thomas
Lim, L.
Raston, C.
Shear induced carboplatin binding within the cavity of a phospholipid mimic for increased anticancer efficacy
title Shear induced carboplatin binding within the cavity of a phospholipid mimic for increased anticancer efficacy
title_full Shear induced carboplatin binding within the cavity of a phospholipid mimic for increased anticancer efficacy
title_fullStr Shear induced carboplatin binding within the cavity of a phospholipid mimic for increased anticancer efficacy
title_full_unstemmed Shear induced carboplatin binding within the cavity of a phospholipid mimic for increased anticancer efficacy
title_short Shear induced carboplatin binding within the cavity of a phospholipid mimic for increased anticancer efficacy
title_sort shear induced carboplatin binding within the cavity of a phospholipid mimic for increased anticancer efficacy
url http://hdl.handle.net/20.500.11937/43632