Pharmaceutical Research

, Volume 20, Issue 10, pp 1626–1633 | Cite as

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


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 1H-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 1H-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.

β-lapachone cyclodextrin inclusion complex solubility bioavailability 


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Copyright information

© Plenum Publishing Corporation 2003

Authors and Affiliations

  • Norased Nasongkla
    • 1
    • 2
  • Andy F. Wiedmann
    • 2
  • Andrew Bruening
    • 3
  • Meghan Beman
    • 3
  • Dale Ray
    • 4
  • William G. Bornmann
    • 5
  • David A. Boothman
    • 3
  • Jinming Gao
    • 2
  1. 1.Department of Macromolecular Science and EngineeringCase Western Reserve UniversityCleveland
  2. 2.Department of Biomedical EngineeringCase Western Reserve UniversityCleveland
  3. 3.Departments of Radiation Oncology and PharmacologyCase Western Reserve UniversityCleveland
  4. 4.Cleveland Center for Structural BiologyCase Western Reserve UniversityCleveland
  5. 5.Preparative Synthesis Core FacilityMemorial Sloan Kettering Cancer CenterNew York

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