title: UV-curable gels as topical nail medicines:In vivo residence, anti-fungal efficacy and influence of gel components on their properties.
abstract: UV-curable gels, used as nail cosmetics for their in vivo durability, were reported to be promising as topical nail medicines. Our first aim was thus to investigate whether such durability applies to drug-loaded formulations. This was found to be true. However, ethanol inclusion in the pharmaceutical formulation (to enable drug loading) reduced the in vivo residence. The second aim was therefore to determine any other effects of ethanol, and if ethanol could be avoided by the choice of monomers. Thus, three methacrylate monomers, ethyl methacrylate, isobornyl methacrylate and 2-hydroxyethyl methacrylate (HEMA) were selected, and their influence on the formulation properties were determined. Ethanol and the methacrylate monomer influenced some (but not all) of the formulation properties. The most significant was that HEMA could dissolve drug and enable the preparation of ethanol-free, drug-loaded formulations, which would benefit in vivo residence. The absence of ethanol reduced drug loading, release and ungual flux, but had no negative impact on the in vitro anti-fungal efficacy. Thus, judicious selection of gel components enabled the exclusion of ethanol. The long in vivo residence, little residual monomers, sufficient ungual permeation and in vitro anti-fungal activity of the gels indicates their potential as anti-onychomycotic topical medicines.
authors.affiliation: UCL School of Pharmacy, 29-39 Brunswick Square, London, WC1N 1AX, UK.
authors.forename: L V
authors.initials: LV
authors.lastname: Kerai
authors.affiliation: UCL School of Pharmacy, 29-39 Brunswick Square, London, WC1N 1AX, UK.
authors.forename: S
authors.initials: S
authors.lastname: Hilton
authors.affiliation: Department of Biological Sciences, Institute of Structural and Molecular Biology, Birkbeck, University of London, Malet Street, London, WC1E 7HX, UK.
authors.forename: M
authors.initials: M
authors.lastname: Maugueret
authors.affiliation: Department of Biological Sciences, Institute of Structural and Molecular Biology, Birkbeck, University of London, Malet Street, London, WC1E 7HX, UK.
authors.forename: B B
authors.initials: BB
authors.lastname: Kazi
authors.affiliation: Department of Biological Sciences, Institute of Structural and Molecular Biology, Birkbeck, University of London, Malet Street, London, WC1E 7HX, UK.
authors.forename: J
authors.initials: J
authors.lastname: Faull
authors.affiliation: Department of Biological Sciences, Institute of Structural and Molecular Biology, Birkbeck, University of London, Malet Street, London, WC1E 7HX, UK.
authors.forename: S
authors.initials: S
authors.lastname: Bhakta
authors.affiliation: UCL School of Pharmacy, 29-39 Brunswick Square, London, WC1N 1AX, UK. Electronic address: s.murdan@ucl.ac.uk.
authors.forename: S
authors.initials: S
authors.lastname: Murdan
mesh_terms: D000287:Administration, Topical; D000293:Adolescent; D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000008:administration & dosage* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D000431:Ethanol / Q000737:chemistry; D005782:Gels / Q000008:administration & dosage* / Q000737:chemistry; D006801:Humans; D008689:Methacrylates / Q000737:chemistry; D008875:Middle Aged; D009262:Nails / Q000187:drug effects*; D010539:Permeability; D014466:Ultraviolet Rays; D055815:Young Adult
chemical_list: D000935:Antifungal Agents; D005782:Gels; D008689:Methacrylates; D000431:Ethanol; C005044:hydroxyethyl methacrylate; C016439:ethyl methacrylate monomer
keywords: Acrylate; Amorolfine; Anti-fungal efficacy; In vivo; Onychomycosis; Permeation; Release; Residence; TOWL; Terbinafine; UV gel; Ungual