Enhancement of Solubility and Bioavailability of β-Lapachone Using Cyclodextrin Inclusion Complexes

Norased Nasongkla, Andy F. Wiedmann, Andrew Bruening, Meghan Beman, Dale Ray, William G. Bornmann, David A. Boothman, Jinming Gao

Research output: Contribution to journalArticlepeer-review

130 Scopus citations


Purpose. To explore the use of cyclodextrins (CD) to form inclusion complexes with β-lapachone (β-lap) to overcome solubility and bioavailability problems previously noted with this drug. Methods. Inclusion complexes between β-lap and four cyclodextrins (α-, β-, γ-, and HPβ-CD) in aqueous solution were investigated by phase solubility studies, fluorescence, and 1 H-NMR spectroscopy. Biologic activity and bioavailability of β-lap inclusion complexes were investigated by in vitro cytotoxicity studies with MCF-7 cells and by in vivo lethality studies with C57Blk/6 mice (18-20 g). Results. Phase solubility studies showed that β-lap solubility increased in a linear fashion as a function of α-, β-, or HPβ-CD concentrations but not γ-CD. Maximum solubility of β-lap was achieved at 16.0 mg/ml or 66.0 mM with HPβ-CD. Fluorescence and 1 H-NMR spectroscopy proved the formation of 1:1 inclusion complexes between β-CD and HPβ-CD with β-lap. Cytotoxicity assays with MCF-7 cells showed similar biologic activities of β-lap in β-CD or HPβ-CD inclusion complexes (TD50 = 2.1 μM). Animal studies in mice showed that the LD50 value of β-lap in an HPβ-CD inclusion complex is between 50 and 60 mg/kg. Conclusions. Complexation of β-lap with HPβ-CD offers a major improvement in drug solubility and bioavailability.

Original languageEnglish (US)
Pages (from-to)1626-1633
Number of pages8
JournalPharmaceutical Research
Issue number10
StatePublished - Oct 1 2003


  • Bioavailability
  • Cyclodextrin
  • Inclusion complex
  • Solubility
  • β-lapachone

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)


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