title: Host-Guest Complexes of Carboxylated Pillar[n]arenes With Drugs.
abstract: Pillar[n]arenes are a new family of nanocapsules that have shown application in a number of areas, but because of their poor water solubility their biomedical applications are limited. Recently, a method of synthesizing water-soluble pillar[n]arenes was developed. In this study, carboxylated pillar[n]arenes (WP[n], n = 6 or 7) have been examined for their ability to form host-guest complexes with compounds relevant to drug delivery and biodiagnostic applications. Both pillar[n]arenes form host-guest complexes with memantine, chlorhexidine hydrochloride, and proflavine by1H nuclear magnetic resonance and modeling. Binding is stabilized by hydrophobic effects within the cavities, and hydrogen bonding and electrostatic interactions at the portals. Encapsulation within WP[6] results in the complete and efficient quenching of proflavine fluorescence, giving rise to "on" and "off" states that have potential in biodiagnostics. The toxicity of the pillar[n]arenes was examined using in vitro growth assays with the OVCAR-3 and HEK293 cell lines. The pillar[n]arenes are relatively nontoxic to cells except at high doses and after prolonged continuous exposure. Overall, the results show that there could be a potentially large range of medical applications for carboxylated pillar[n]arene nanocapsules.
authors: Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia. Electronic address: nial.wheate@sydney.edu.au.
authors: Nial J
authors: NJ
authors: Wheate
authors: Hormones and Cancer Group, Kolling Institute of Medical Research, Royal North Shore Hospital, University of Sydney, St Leonards, NSW 2065, Australia.
authors: Kristie-Ann
authors: KA
authors: Dickson
authors: Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia.
authors: Ryung Rae
authors: RR
authors: Kim
authors: Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia.
authors: Alireza
authors: A
authors: Nematollahi
authors: School of Chemistry, University of Sydney, Sydney, NSW 2006, Australia.
authors: René B
authors: RB
authors: Macquart
authors: Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia.
authors: Veysel
authors: V
authors: Kayser
authors: State Key Laboratory of Chemical Engineering, Department of Chemistry, Zhejiang University, Hangzhou 310027, People's Republic of China.
authors: Guocan
authors: G
authors: Yu
authors: Faculty of Pharmacy, University of Sydney, Sydney, NSW 2006, Australia.
authors: W Bret
authors: WB
authors: Church
authors: Hormones and Cancer Group, Kolling Institute of Medical Research, Royal North Shore Hospital, University of Sydney, St Leonards, NSW 2065, Australia.
authors: Deborah J
authors: DJ
authors: Marsh
mesh_terms: D057809:HEK293 Cells; D006801:Humans; D046911:Macromolecular Substances / Q000737:chemistry / Q000378:metabolism*; D008559:Memantine / Q000378:metabolism; D008958:Models, Molecular; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000378:metabolism*; D011370:Proflavine / Q000737:chemistry / Q000378:metabolism; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000378:metabolism*
chemical_list: D046911:Macromolecular Substances; D004364:Pharmaceutical Preparations; D000644:Quaternary Ammonium Compounds; D011370:Proflavine; D008559:Memantine
keywords: biodiagnostics; drug delivery; excipient; fluorescence; host-guest; molecular modeling; nanocapsule; pharmaceutics; pillar[n]arene