Assessing The Potential Wound Healing Abilities Of Ciclopirox

By Gary L. Dockery, DPM, FACFAS

   Ciclopirox has been well documented as a broad-spectrum antifungal agent with additional antibacterial and antiinflammatory properties.1-3 However, in recent studies reported by Linden, et al., ciclopirox has also demonstrated potent angiogenic activity, which suggests that the drug may have certain wound-healing properties.4 If this is borne out by larger studies in the future, ciclopirox may possess a significant advantage in treating fungal infections in high-risk patients.

   These high-risk patients may include those who suffer from diabetes mellitus and peripheral vascular disease, as well as those with autoimmune disorders such as AIDS or HIV infection. Other high-risk patients include the elderly, particularly those in nursing homes, those with poor hygiene, substance abusers and those on long-term therapies with antibiotics, corticosteroids, chemotherapy or radiation.5

   Given that this population exhibits a greater tendency for serious lower-extremity complications from foot infections and chronic ulcers, clinicians may want to re-evaluate treating fungal infections (both simple and complex) with ciclopirox in light of these new findings regarding the drug’s potential for wound healing.

   In earlier studies addressing the cutaneous effects of a 1% ciclopirox solution on rabbit skin, Linden, et al., observed occasionally transient reddening of healthy skin and persistent reddening of experimentally wounded skin. This observation prompted their investigation of the capability of ciclopirox to induce angiogenesis.4

   Therapeutic angiogenesis, whether it occurs via recombinant angiogenic growth factors or by gene therapy, has become an important treatment modality during the past few years.6-8 The hypoxia-inducible factor (HIF)-1 is a physiological regulator of vascular endothelial growth factor (VEGF) expression. The Linden studies explored the possibility that ciclopirox activates endogenous HIF-1 target genes — including VEGF — in in vitro cell culture and in vivo organ models. These studies uncovered a potent angiogenic activity of ciclopirox.4

    (In ongoing human clinical trials, researchers have applied VEGF gene therapy in the treatment of critical limb ischemia and myocardial ischemia. In experimental investigations, researchers have looked at VEGF therapy for treating gastric and duodenal ulcerations, as well as in dermal ulcers, cultured skin substitutes and skin excision wounds.9-14)

What Studies Reveal About Ciclopirox

   Let’s take a closer look at the ciclopirox studies by Linden, et al.4

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