Bioadhesive patch-based delivery of 5-aminolevulinic acid to the nail for photodynamic therapy of onychomycosis
Bioadhesive patch-based delivery of 5-aminolevulinic acid to the nail for photodynamic therapy of onychomycosis
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DOI：
10.1016/j.jconrel.2004.12.005
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发表时间：
2005-03-21
影响因子：
10.8
通讯作者：
Woolfson, AD
中科院分区：
文献类型：
--
作者：
Donnelly, RF;McCarron, PA;Woolfson, AD
描述了5-氨基乙酰丙酸（ALA）从含50 mg cm（-2）ALA的新型生物粘附贴片释放时，通过人指甲和新生猪蹄的体外渗透。ALA是光敏剂原卟啉IX（PpIX）的天然前体。过量ALA的局部应用绕过负反馈抑制，并在应用部位产生光敏浓度的PpIX。基于ALA的光动力疗法（PDT）已在各种皮肤肿瘤的局部治疗中被广泛研究。最近，它的应用已扩展到微生物领域。如果能够在甲基质和甲床中获得足够浓度的ALA，PDT可能被证明是甲真菌病的有效治疗方法。贴片应用24小时允许ALA浓度为2.8 mM，以实现对切除的人指甲的腹侧。应用48 h诱导的浓度为6.9 mM。应用时间对新生猪中平均深度为2.375 mm的ALA浓度没有显著影响，应用时间为24、48和72 h均产生0.1 mM的浓度。分别导致87%和42%的活力减少，分别用红光照射后。与0.1 mM ALA孵育30分钟和6小时，分别导致32%的白念珠菌和6%的趾间毛癣菌，照射后的活力减少。可以使用渗透促进剂或通过填充指甲的不可渗透的背表面来改善药物穿过指甲的渗透。此外，铁螯合剂可用于增加给定ALA剂量的PpIX产生。因此，通过适当的修改，ALA-PDT可能被证明是一个可行的替代治疗甲真菌病。(c)2005 Elsevier B. V.保留所有权利。
The in vitro penetration of 5-aminolevulinic acid (ALA) across human nail and into neonate porcine hoof when released from a novel bioadhesive patch containing 50 mg cm(-2) ALA is described. ALA is a naturally occurring precursor of the photosensitiser protoporphyrin IX (PpIX). Topical application of excess ALA bypasses negative feedback inhibition and yields photosensitising concentrations of PpIX at the application site. ALA-based photodynamic therapy (PDT) has been extensively investigated in the topical treatment of various skin neoplasias. Recently, its use has been extended to the microbiological field. If sufficient concentrations of ALA could be achieved within the nail matrix, and at the nail bed, PDT may prove to be a useful treatment for onychomycosis. Patch application for 24 h allowed an ALA concentration of 2.8 mM to be achieved on the ventral side of excised human nail. Application for 48 h induced a concentration of 6.9 mM. Application time had no significant effect on the ALA concentration at mean depths of 2.375 mm in neonate porcine, with application times of 24, 48 and 72 h all producing concentrations of 0.1 mM. Incubation of Candida albicans and Trichophyton interdigitale with ALA concentrations of 10.0 mM for 30 min and 6 h, respectively, caused reductions in viability of 87% and 42%, respectively, following irradiation with red light. Incubation with 0.1 mM ALA for 30 min and 6 h, respectively, caused reductions in viability of 32% for Candida albicans and 6% for Trichophyton interdigitale, following irradiation. Drug penetration across nail may be improved using penetration enhancers, or by filing of the impenetrable dorsal surface of the nail. Moreover, iron chelators can be used to increase PpIX production for a given ALA dose. Therefore, with suitable modifications, ALA-PDT may prove to be a viable alternative in the treatment of onychomycosis. (c) 2005 Elsevier B.V. All rights reserved.