Modulating β-lapachone release from polymer millirods through cyclodextrin complexation

Fangjing Wang, Elvin Blanco, Hua Ai, David A. Boothman, Jinming Gao

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


β-Lapachone (β-lap) is a novel anticancer agent that kills tumors overexpressing the NADP(H): quinone oxidoreductase enzyme. However, poor aqueous solubility and low bioavailability hinder its therapeutic applications. Herein we describe the development of poly(D,L-lactide-co-glycolide) (PLGA) polymer millirods for local delivery of β-lap. The objective was to investigate the use of β-lap inclusion complexes with cyclodextrins (CDs) to control β-lap release kinetics from PLGA millirods. Differential scanning calorimetry was performed to measure drug/polymer interactions, complexation efficiency with different CDs, and complex/polymer interactions. β-Lap was found to have a solid-state solubility of 13% in PLGA. β-Lap dissolution in PLGA matrix lowered the glass transition temperature of PLGA from 44 to 31°C, and led to a slow release of β-lap (8.8 ± 1.2% release after 22 days). For β-lap and CD interactions, increasing complexation efficiency was observed in the order of α-CD, γ-CD, and β-CD, β-Lap complexation with hydroxypropyl-β-cyclodextrin (HPβ-CD) prevented drug dissolution in PLGA, and led to fast release (79.6 ± 2.1% after 2 days). Sustained drug release was achieved when β-lap was complexed with α-CD or γ-CD. These data demonstrate the ability to tailor β-lap release kinetics via CD complexation, providing exciting opportunities for the use of β-lap-millirods for intratumoral drug delivery.

Original languageEnglish (US)
Pages (from-to)2309-2319
Number of pages11
JournalJournal of Pharmaceutical Sciences
Issue number10
StatePublished - Oct 2006


  • β-lapachone
  • Cyclodextrin inclusion complexation
  • Drug delivery
  • Drug-polymer interactions
  • Poly(lactic/glycolic) acid (PLGA)

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science


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