title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: a 1 Department of Plastic Surgery.
authors.forename: Yong-Hong
authors.initials: YH
authors.lastname: Qin
authors.affiliation: b 2 Department of Pharmacy, Second Hospital of Lanzhou University , Lanzhou, Gansu Province, PR China.
authors.forename: Hai-Sheng
authors.initials: HS
authors.lastname: Jiao
authors.affiliation: c 3 Health Center for Women and Children of An Ding District , Ding Xi City, Gansu Province, PR China.
authors.forename: Ai-Shu
authors.initials: AS
authors.lastname: Li
authors.affiliation: b 2 Department of Pharmacy, Second Hospital of Lanzhou University , Lanzhou, Gansu Province, PR China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Jiao
authors.affiliation: b 2 Department of Pharmacy, Second Hospital of Lanzhou University , Lanzhou, Gansu Province, PR China.
authors.forename: Li-Ming
authors.initials: LM
authors.lastname: Wei
authors.affiliation: a 1 Department of Plastic Surgery.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: a 1 Department of Plastic Surgery.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhong
authors.affiliation: a 1 Department of Plastic Surgery.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.affiliation: a 1 Department of Plastic Surgery.
authors.forename: Xuan-Fen
authors.initials: XF
authors.lastname: Zhang
mesh_terms: D000279:Administration, Cutaneous; D017311:Amlodipine / Q000494:pharmacology*; D000818:Animals; D017963:Azithromycin / Q000494:pharmacology*; D016009:Chi-Square Distribution; D004359:Drug Therapy, Combination; D005782:Gels; D006085:Graft Survival; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007511:Ischemia / Q000517:prevention & control; D051381:Rats; D018570:Risk Assessment; D013524:Surgical Flaps / Q000098:blood supply* / Q000382:microbiology; D013530:Surgical Wound Infection / Q000175:diagnosis / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D005782:Gels; D006495:Heparin, Low-Molecular-Weight; D017311:Amlodipine; D017963:Azithromycin
keywords: Azithromycin; amlodipine; infection; ischaemia; low molecular weight heparin; necrosis; skin flap; transdermal penetration