European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences · 2018
Two strategies to enhance ungual drug permeation from UV-cured films: Incomplete polymerisation to increase drug release and incorporation of chemical enhancers.
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Kerai Laxmi Valji, Bardés Josep, Hilton Stephen, Murdan Sudaxshina
Аннотация
UV-curable gels, which polymerise into long-lasting films upon exposure to UVA, have been identified as potential topical drug carriers for the treatment of nail diseases. Limitations of such films include incomplete drug release and low ungual drug permeation. The aim of the work herein was therefore to investigate two strategies, namely: (1) increasing drug release from the film, and (2) increasing nailplate permeability, with the ultimate goal of enhancing ungual drug permeation. To increase drug release via Strategy 1, a UV-LED lamp (whose emitted light was suboptimal for gel polymerisation) was used, and it was hypothesised that such a lamp would result in films that are less polymerised/cross-linked and where the drugs are less 'trapped'. Indeed, the suboptimal lamp influenced polymerisation, such that the films were thinner, had lower glass transition temperatures and enabled a slightly greater (by 15%) drug release of one of the two drugs tested. However, the greater drug release had only a modest impact on ungual drug permeation. To evaluate Strategy 2, i.e. increase nailplate permeability, chemical ungual enhancers, 2-mercaptoethanol (ME), 2-methyl pyrrolidone (NMP), PEG 200 and water were incorporated within the UV-cured films. These chemicals caused increased ungual drug permeation, with ME showing the greatest (by 140%), and water showing the least (by 20%) increase in the amount of drug permeated by day 30. Surprisingly, these chemicals also caused increased drug release from the films, with ME once again having the greatest effect (by 51%) and water the least effect (by 12%). It seems that these chemicals were increasing ungual drug permeation via their influence on drug release (i.e. via their impact on the film) as well as via their influence on the nail itself. We conclude that, of the two strategies tested, the second strategy proved to be more successful at enhancing ungual drug permeation.
Предметные рубрики MeSH
Absorption, PhysiologicalAdministration, TopicalAdolescentAdultAgedDrug CarriersDrug CompoundingDrug LiberationHumansKineticsMercaptoethanolMethacrylatesMiddle AgedMorpholinesNailsPermeabilityPolyethylene GlycolsPolymerizationPolymersPyrrolidinesSolubilityTechnology, PharmaceuticalTerbinafineUltraviolet RaysUrethaneWaterYoung Adult