Abstract：
Conventional treatments for cutaneous leishmaniasis, a neglected vector-borne infectious disease, can frequently lead to serious adverse effects. Paromomycin (PAR), an aminoglycoside antibiotic, has been suggested for the topical treatment of disease-related lesions, but even when formulated in high drug-loading dosage forms, presents controversial efficacy. The presence of five ionizable amino groups hinder its passive cutaneous penetration but make PAR an excellent candidate for iontophoretic delivery. The objective of this study was to verify the feasibility of using iontophoresis for cutaneous PAR delivery and to propose a topical passive drug delivery system that could be applied between iontophoretic treatments. For this, in vitro iontophoretic experiments evaluated different application durations (10, 30, and 360 min), current densities (0.1, 0.25, and 0.5 mA/cm2), PAR concentrations (0.5 and 1.0 %), and skin models (intact and impaired porcine skin). In addition, 1 % PAR hydrogel had its penetration profile compared to 15 % PAR ointment in passive transport. Results showed iontophoresis could deliver suitable PAR amounts to dermal layers, even in short times and with impaired skin. Biodistribution assays showed both iontophoretic transport and the proposed hydrogel delivered higher PAR amounts to deeper skin layers than conventional ointment, even though applying 15 times less drug. To our knowledge, this is the first report of PAR drug delivery enhancement by iontophoresis. In summary, the association of iontophoresis with a topical application of PAR gel seems appropriate for improving cutaneous leishmaniasis treatment.
摘要：
皮肤利什曼病的常规治疗，一种被忽视的媒介传播传染病，经常会导致严重的不良反应。巴龙霉素(PAR),一种氨基糖苷类抗生素,已被建议用于疾病相关病变的局部治疗，但即使配制成高载药量的剂型，提出了有争议的功效。五个可电离的氨基的存在阻碍了其被动的皮肤渗透，但使PAR成为离子电渗递送的优秀候选物。这项研究的目的是验证使用离子电渗疗法进行皮肤PAR递送的可行性，并提出一种可在离子电渗治疗之间应用的局部被动药物递送系统。为此，体外离子电渗实验评估了不同的应用持续时间（10、30和360分钟），电流密度（0.1、0.25和0.5mA/cm2），PAR浓度（0.5和1.0%），和皮肤模型（完整和受损的猪皮肤）。此外,与被动转运中的15%PAR软膏相比,1%PAR水凝胶具有其渗透曲线。结果表明，离子电渗疗法可以将合适的PAR量输送到真皮层，即使在短时间内和皮肤受损。生物分布分析显示，离子电渗转运和拟议的水凝胶比常规软膏向更深的皮肤层递送更高的PAR量。即使应用少15倍的药物。据我们所知,这是离子电渗疗法增强PAR药物递送的首次报道。总之,离子电渗疗法与局部应用PAR凝胶的联合似乎适合改善皮肤利什曼病的治疗。
