Demonstration of in vitro host-guest complex formation and safety of para-sulfonatocalix[8]arene as a delivery vehicle for two antibiotic drugs

Yvonne E. Moussa, Yu Qing Elysia Ong, John D. Perry, Zhengqi Cheng, Veysel Kayser, Esteban Cruz, Ryung Rae Kim, Natasha Sciortino, Nial J. Wheate*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

The macrocycle para-sulfonatocalix[8]arene, sCX[8], was examined with 2 antibiotic drugs, ciprofloxacin (CIP) and isoniazid. The drugs were shown to form complexes with sCX[8] using proton nuclear magnetic resonance, thermogravimetric analysis, fluorescence spectroscopy, and molecular modeling. Both drugs form 1:1 hydrated (H2O: 13%-14% w/w) host-guest complexes, with sCX[8] binding around the pyridine ring of isoniazid, and around the piperazine and cyclopropane rings of CIP. From proton nuclear magnetic resonance, the binding constant of isoniazid to sCX[8] was 6.8 (±0.3) × 103 M−1. Addition of 2 equivalents of sCX[8] to CIP resulted in a 58% decrease in fluorescence, and time-resolved fluorescence anisotropy of CIP doubles with sCX[8]. Each drug binds into the cavity of the macrocycle, with binding stabilized via combinations of hydrogen bonding, electrostatic interactions, π-π stacking, and hydrophobic effects. The safety of sCX[8] was examined in vitro with human embryonic kidney 293 cells. The IC50 of sCX[8] was 559 μM, which is a minimum of 5-fold higher than the concentration that would be used in the clinic. The in vitro effect of sCX[8] on the action of CIP was examined on a panel of bacterial lines. The results showed that sCX[8] has no inherent antibiotic activity and had no negative effect on the action of CIP.

Original languageEnglish
Pages (from-to)3105-3111
Number of pages7
JournalJournal of Pharmaceutical Sciences
Volume107
Issue number12
DOIs
Publication statusPublished - Dec 2018
Externally publishedYes

Keywords

  • antibiotic
  • calixarene
  • ciprofloxacin
  • drug delivery
  • host-guest
  • isoniazid

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