Onychomycosis (OM) is a fungal infection, responsible for about 50% of nail diseases. OM has been attributed to the ability of fungi to naturally organize themselves into biofilms on nail surfaces. However, little is known about the exact role of the biofilm in the etiopathogenesis of OM, as well as its influence in the permeation of a topical treatment. The objectives of this study were to review the literature for topical OM treatments in clinical trials, assess the efficiency of these treatments, and discuss factors that could affect the success of these treatments. First, a systematic search of articles published in the MEDLINE database (PubMed) between January 2010 and December 2019 was conducted, focusing on drugs under clinical trials for the topical treatment of OM. Of the publications selected, it was clear that none of them had considered the fungi organized in biofilm. Therefore, we reflected on some important variables involved in OM, such as the nail structure and the mechanism of fungal invasion. Some methods, such as histopathologic analysis and spectroscopy techniques, were found to be effective in the detection of nail biofilm, and could be used in future drug permeation studies. This review allowed us to conclude that novel antifungals for the topical treatment of OM must consider the drug to permeate through biofilm. Natural products, such as propolis, seem strong candidates in this respect.
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