In Vitro penetration of a novel oxaborole antifungal (AN2690) into the human nail plate.
Onychomycosis is a challenging fungal infection to treat topically, likely due to the unique properties of the nail plate. This seemingly impenetrable barrier has high resistance to the passage of antifungal drugs in sufficient concentrations to kill the causative fungi deep in the nail bed. Recently, a new class of antifungal agent was described, termed oxaboroles, which have broad-spectrum activity. These oxaboroles were designed with properties believed to be required to allow for easier transit through the nail plate. Herein, we report (i) the nail penetration results of four oxaboroles that led to the selection of AN2690, (ii) the results of the nail penetration of AN2690 from four vehicles, and (iii) the nail penetration of AN2690 in its chosen vehicle compared to a commercial control, ciclopirox. AN2690 has superior penetration compared to ciclopirox, and achieves levels within and under the nail plate that suggest it has the potential to be an effective topical treatment for onychomycosis.
Hui
Xiaoying
X
Department of Dermatology, University of California San Francisco, Box 0989, 90 Medical Center Way, San Francisco, California 94143, USA. huix@derm.ucsf.com
Baker
Stephen J
SJ
Wester
Ronald C
RC
Barbadillo
Sherry
S
Cashmore
Anne K
AK
Sanders
Virginia
V
Hold
Karin M
KM
Akama
Tsutomu
T
Zhang
Yong-Kang
YK
Plattner
Jacob J
JJ
Maibach
Howard I
HI
D000935:Antifungal Agents / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D001896:Boron Compounds / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical; D000077768:Ciclopirox; D004058:Diffusion; D015194:Diffusion Chambers, Culture; D004339:Drug Compounding; D000431:Ethanol / Q000737:chemistry; D006229:Hand Dermatoses / Q000188:drug therapy; D006801:Humans; D015394:Molecular Structure; D009262:Nails / Q000378:metabolism*; D014009:Onychomycosis / Q000188:drug therapy; D010539:Permeability; D014677:Pharmaceutical Vehicles / Q000737:chemistry; D010865:Pilot Projects; D019946:Propylene Glycol / Q000737:chemistry; D011728:Pyridones / Q000378:metabolism; D012995:Solubility; D013997:Time Factors
D000935:Antifungal Agents; D001896:Boron Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D014677:Pharmaceutical Vehicles; D011728:Pyridones; D000077768:Ciclopirox; D000431:Ethanol; D019946:Propylene Glycol; C512998:tavaborole