Transdermal application of azithromycin-amlodipine-heparin gel enhances survival of infected random ischaemic flap

Abstract

Background: Flap necrosis is generally regarded as the result of vasospasm, thrombosis, and infection. Methods: To improve skin flap survival and lower the risk of side effects due to systemic drug delivery, we formulated and evaluated compound gels for transdermal application. The transdermal delivery of 1% azithromycin (AZM), 0.5% amlodipine besylate (AB), and 300 IU/g low molecular weight heparin (LMWH) in compound gels, singly or in combinations, was measured across rat skin in vitro. The effects of AB and LMWH on flap blood circulation was investigated using fluorescein angiography, by transdermally applying the gel onto the surface of an in vivo ischaemic flap rat model; concentrations of the drugs were detected in both blood plasma and flap tissue at assigned timepoints. Finally, infected ischaemic flaps were treated to evaluate their anti-inflammatory effects and sizes of flap survival area. Results: Each drug efficiently penetrated the in vitro skin in a time-dependent manner. In the in vivo ischaemic flaps, AB or LMWH increased the blood supply. All gel formulations that included AZM were associated with less flap inflammation. The surviving areas after treatment with AZM+LMWH or AZM+AB were significantly larger than that treated with the AZM-only gel, and the largest surviving area was that treated with AZM+AB+LMWH. Gels containing no AZM could not decrease flap inflammation or increase flap survival. Conclusion: Transdermal application of a compound gel with AZM, AB, and LMWH combined is a promising method to prevent and treat flap infection, improve blood circulation, and increase the survival of infected ischaemic flaps.

Key Words:

• Azithromycin
• amlodipine
• low molecular weight heparin
• transdermal penetration
• skin flap
• infection
• ischaemia
• necrosis

Acknowledgement

This article should be attributed to the Department of Plastic Surgery, Second Hospital of Lanzhou University, Lanzhou 730030, Gansu Province, PR China.

Funding: The financial support from medical research funds of Lanzhou University (Grant LZUYX200822), and the Lanzhou University, Second Hospital (YJ 2010-20).

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.