title: Shear induced carboplatin binding within the cavity of a phospholipid mimic for increased anticancer efficacy.
abstract: 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 IC50 concentration by 10 fold, and markedly increased the percent of cells in the S-phase (DNA replication) of the cell cycle.
authors.affiliation: Pharmacy, School of Medicine and Pharmacology, The University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia.
authors.forename: Jingxin
authors.initials: J
authors.lastname: Mo
authors.affiliation: 1] Centre for NanoScale Science and Technology, School of Chemical and Physical Sciences, Flinders University, Bedford Park, SA, 5042, Australia [2] School of Chemistry and Biochemistry, The University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia.
authors.forename: Paul K
authors.initials: PK
authors.lastname: Eggers
authors.affiliation: Centre for NanoScale Science and Technology, School of Chemical and Physical Sciences, Flinders University, Bedford Park, SA, 5042, Australia.
authors.forename: Xianjue
authors.initials: X
authors.lastname: Chen
authors.affiliation: Pharmacy, School of Medicine and Pharmacology, The University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia.
authors.forename: Muhammad Rizwan Hussain
authors.initials: MR
authors.lastname: Ahamed
authors.affiliation: Nanochemistry Research Institute, Department of Chemistry, Curtin University, Perth, WA 6845, Australia.
authors.forename: Thomas
authors.initials: T
authors.lastname: Becker
authors.affiliation: Pharmacy, School of Medicine and Pharmacology, The University of Western Australia, 35 Stirling Highway, Crawley, WA, 6009, Australia.
authors.forename: Lee
authors.initials: L
authors.lastname: Yong Lim
authors.affiliation: Centre for NanoScale Science and Technology, School of Chemical and Physical Sciences, Flinders University, Bedford Park, SA, 5042, Australia.
authors.forename: Colin L
authors.initials: CL
authors.lastname: Raston
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D047250:Calixarenes / Q000138:chemical synthesis / Q000737:chemistry*; D016190:Carboplatin / Q000737:chemistry* / Q000633:toxicity; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry; D065546:Drug Liberation; D059585:G1 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010743:Phospholipids / Q000737:chemistry*; D033081:Shear Strength
chemical_list: D000970:Antineoplastic Agents; D004337:Drug Carriers; D010743:Phospholipids; D047250:Calixarenes; D016190:Carboplatin