Transdermal delivery of heparin and low-molecular weight heparin using low-frequency ultrasound

S. Mitragotri, J. Kost

Research output: Contribution to journalArticlepeer-review

107 Scopus citations


Purpose. Heparin and low-molecular weight heparin (LMWH) are the most commonly used anticoagulants and are administered by intravenous or subcutaneous injections. However, injections of heparin have the potential risk of bleeding complications and the requirement of close monitoring in some cases. We hypothesized that transdermal delivery of heparin may provide an attractive alternative to injections. However, the dose of transdermally delivered heparin is limited by low skin permeability. Methods. We increased skin permeability to heparin and LMWH using low-frequency (20 kHz) ultrasound. Biologic activity of transdermally delivered heparin was measured by using activated clotting time assays and by using anti-Xa (aXa) activity. Structural integrity of heparin was also assessed by using gel electrophoresis. Results. Low-frequency ultrasound increased permeability of pigskin in vitro and rat skin in vivo and allowed delivery of biologically active doses of heparin and low-molecular weight heparin transdermally. A prolonged contact of transdermally delivered heparin with pigskin was found to reduce the biologic activity of heparin, although no such deactivation was observed during short exposures. Transdermally delivered LMWH resulted in sustained aXa levels in the blood. This result was in strong contrast to subcutaneous or intravenous injections of LMWH, which resulted in only temporary elevations of aXa level. Conclusions. Transdermal delivery of low-molecular weight heparin is a potential alternative to injections.

Original languageEnglish
Pages (from-to)1151-1156
Number of pages6
JournalPharmaceutical Research
Issue number8
StatePublished - 8 Oct 2001


  • Heparin
  • Low-molecular weight heparin
  • Sonophoresis
  • Thrombosis
  • Ultrasound

ASJC Scopus subject areas

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


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