Assessing The Potential Wound Healing Abilities Of Ciclopirox

By Gary L. Dockery, DPM, FACFAS
   • Does ciclopirox induce angiogenesis in the chicken chorioallantoic membrane (CAM)? Based on the investigators’ observations that ciclopirox induced VEGF expression in cell culture, they analyzed its angiogenic capacity in an in vivo model of angiogenesis. At day nine of development, researchers overlaid the chicken CAM with inert polymer discs containing various concentrations of ciclopirox or solvent only. After two days of incubation, researchers observed no signs of angiogenesis with the solvent control discs.    In contrast, polymer discs containing 50 µM ciclopirox consistently induced CAM angiogenesis, as evidenced by numerous, newly formed, radially arranged vessels. A total of 10 CAMs treated with 50 µM ciclopirox showed similar angiogenesis and all seven control CAMs lacked any signs of angiogenesis. Investigators noted that the 1% ciclopirox concentration in dermal cream equals a molar concentration of 37 µM, which is close to the concentration found to be angiogenic in these CAM assays.

What One Can Draw From The Linden Studies

   The Linden studies demonstrate that ciclopirox functionally activates HIF-1 and induces VEGF transcription as well as angiogenesis. The authors observed that wound healing in the skin may be complicated by microbial invasion, inflammation and ischemia, leading to ulceration. As ciclopirox is lipophilic, antimicrobiotic, antiinflammatory, angiogenic and does not affect healthy tissue, it might be beneficial for the topical treatment of skin wound tissue.4    The implications of potential wound-healing properties in the antifungal ciclopirox are especially noteworthy for podiatrists who are all too familiar with the various simple and complex infections that can lead to chronic wounds (see “Understanding The Connection Between Common Infections And Chronic Wounds” below). These infections result from a combination of factors including disease, injury, neuropathy, vascular impairment and inefficient wound healing. Severe complications leading to wounds in the feet and lower leg occur as a result of chronic infections, pathogenic resistance to drugs and lack of treatment.21,22

Understanding The Connection Between Common Infections And Chronic Wounds

   The incidence of severe and chronic wounds among patients with diabetes has risen dramatically in the United States. Type 1 and 2 diabetes afflict an estimated 17 million people and up to 15 percent of those patients will undergo lower-extremity amputation.23,24 Public health officials estimate 800,000 new cases of diabetes are diagnosed annually. Diabetes patients will undergo lower-extremity amputations at an increasing rate, with approximately 80 percent of those amputations primarily caused by chronic foot ulcers.23-25    Similar to patients with diabetes, those with peripheral vascular disease and those who are immunocompromised frequently suffer lower extremity complications because of fungal and bacterial infections.    Three of the most common clinical presentations podiatrists see are tinea pedis, onychomycosis and paronychia. Dermatophytes are commonly the underlying basis for tinea pedis and other fungal and bacterial infections.26 Although nail infections are preceded by a dermatophyte, the symptomatic patient may have a more complex infection, complicated by pyogenic bacteria or other fungal species.27    Currently, ciclopirox is indicated for topical treatment of a broad range of dermal fungal infections including: tinea pedis, tinea cruris and tinea corporis due to Trichophyton rubrum, T. mentagrophytes, Epidermophyton floccosum and Microsporum canis; candidiasis due to Candida albicans; and tinea versicolor due to Malassezia furfur.1,28 Ciclopirox also has in vitro activity against many Gram-positive and Gram-negative bacteria including Escherichia coli, Proteus mirabilis, Pseudomonas aeruginosa, and Staphylococcus and Streptococcus species.2 There is also evidence that ciclopirox may exhibit better antiinflammatory activity than 2.5% hydrocortisone.3

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