Human nail plate modifications induced by onychomycosis: implications for topical therapy.

Human nail plate modifications induced by onychomycosis: implications for topical therapy.
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DOI:
10.1007/s11095-014-1562-5
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发表时间:
2015-05
影响因子:
3.7
通讯作者:
Murdan, S.
Murdan, S.
中科院分区:
医学3区
文献类型:
--
作者:
Baraldi, A.;Jones, S. A.;Guesne, S.;Traynor, M. J.;McAuley, W. J.;Brown, M. B.;Murdan, S.

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通过人类真菌指甲板的特征,本研究旨在为新的局部掌形制剂的设计提供信息。人类指甲的机械性能是用劳埃德拉伸强度测试仪表征。用密度仪测定甲的密度,用电镜观察甲的超微结构。拉曼光谱分析了指甲内的角蛋白二硫化物键,并通过定量水和罗丹明摄取来评估其渗透性。慢性体内甲板感染使人甲板厚度(健康者0.49±0.15 mm,患病者1.20±0.67 mm)增加,但抗拉强度(健康者63.7±13.4 MPa,患病者41.7±5.0 MPa)和密度(健康者1.34±0.01 g/cm3,患病者1.29±0.00 g/cm3)降低。盘菌病引起细胞-细胞分离,但不破坏甲二硫键或桥粒。患病指甲和健康指甲表现出相同的吸水曲线,但使用PBS载体的患病指甲的罗丹明穿透率高4倍,使用乙醇/PBS载体的罗丹明穿透率高3倍。瘤菌指甲呈现出更厚但更多孔的屏障,其侵蚀的细胞内基质使组织对局部应用的化学物质更具渗透性。本文的在线版本(doi:10.1007/s11095-014-1562-5)包含补充资料,仅供授权用户使用。
Through the characterisation of the human onchomycotic nail plate this study aimed to inform the design of new topical ungual formulations. The mechanical properties of the human nail were characterised using a Lloyd tensile strength tester. The nail’s density was determined via pycnometry and the nail’s ultrastructure by electron microscopy. Raman spectroscopy analysed the keratin disulphide bonds within the nail and its permeability properties were assessed by quantifying water and rhodamine uptake. Chronic in vivo nail plate infection increased human nailplate thickness (healthy 0.49 ± 0.15 mm; diseased 1.20 ± 0.67 mm), but reduced its tensile strength (healthy 63.7 ± 13.4 MPa; diseased 41.7 ± 5.0 MPa) and density (healthy 1.34 ± 0.01 g/cm3; diseased 1.29 ± 0.00 g/cm3). Onchomycosis caused cell-cell separation, without disrupting the nail disulfide bonds or desmosomes. The diseased and healthy nails showed equivalent water uptake profiles, but the rhodamine penetration was 4-fold higher in the diseased nails using a PBS vehicle and 3 -fold higher in an ethanol/PBS vehicle. Onchomycotic nails presented a thicker but more porous barrier, and its eroded intracellular matrix rendered the tissue more permeable to topically applied chemicals when an aqueous vehicle was used. The online version of this article (doi:10.1007/s11095-014-1562-5) contains supplementary material, which is available to authorized users.
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