Overcoming nail barrier properties in onychomycosis treatment

Onychomycosis is the most common nail infection and extremely difficult to treat due
to the thick keratin barrier of the nail plate. Conventional topical therapies such as
ciclopirox, terbinafine, and amorolfine require prolonged use and show low cure rates.
Our wool keratin studies revealed that ciclopirox binds more strongly to keratin than
the others, potentially reducing its free drug availability and antifungal efficacy in
keratin-rich environments like nails. Nail plate poration is being explored to enhance
drug delivery, but its effectiveness with current antifungals needs further study. This
project aims to mechanically porate human nails; initially using skin poration devices
as proof of concept, followed by custom-designed tools. Fungal infection and drug
penetration will be assessed using confocal Raman microscopy, and infected nail
microstructure examined via SEM.
The aim of microneedle poration is to create an array of microchannels in the nail
plate, potentially increasing drug uptake. Raman spectra could reveal distinct peaks
representing infected or healthy nail; therefore, effective treatment could be non-
invasively identified. We expect nail poration to improve antifungal flux and reduce
treatment frequency, resulting in better infection control. Raman spectra also assist in
differentiating infected from healthy nails by keratin signal alterations on the disulfide (S-S) bonds. These observations highlight Raman microscopy’s potential for rapid, non-invasive diagnosis and monitoring of treatment progress. Additionally, SEM
imaging of infected nails is expected to reveal extensive hyphal networks penetrating
the nail plate.
In summary, this innovative combination of nail poration and conventional antifungals could significantly improve intra-nail drug concentrations. While the poration approach could result in larger drug permeation, advanced imaging provides critical insights into infection status and drug distribution.