Postgraduate Program in Pharmacy (PGFar), Federal University of Santa Catarina, Trindade, SC, 88040-900, Florianopolis, Brazil.
Pharm Res. 2020 Nov 9;37(12):240. doi: 10.1007/s11095-020-02951-4.
Dapsone (DAP) is a long-established molecule that remains a promising therapeutic agent for various diseases mainly because it combines antimicrobial and anti-inflammatory activities. Its oral application, however, is limited by the dose-dependent hematological side effects that may rise from systemic exposure. As an alternative to overcome this limitation, the administration of DAP to the skin has witnessed prominent interest in the past 20 years, particularly when applied to the treatment of dermatological disorders. In this review, all technological strategies proposed to the topical delivery of DAP are presented. Most of the reported studies have been devoted to the clinical use and safety of a gel formulation containing both solubilized and microcrystalline drug, however, the technological characteristics of such preparation are still missing. In parallel, the incorporation of DAP into vesicular and particulate carriers (e.g. nano- and microemulsions, niosomes, invasomes, bilosomes, cubosomes, solid lipid nanoparticles, nanostructured lipid carriers, polymeric nanocapsules and polymer-lipid-polymer hybrid nanoparticles) appears to be an alternative to provide greater drug release control, enhanced drug solubilization and follicular targeting. Indeed, the main application of DAP topical formulations reported in the literature was the treatment of acne vulgaris, a disease located in the hair follicle. Other diseases affecting different regions of the skin (e.g. cutaneous lupus erythematosus and cutaneous leishmaniasis), however, may also benefit from a topical therapeutic regimen containing DAP. Therefore, the investigation of appendageal route in comparison to passive transmembrane diffusion as a function of targeted disease, as well as pharmacokinetic studies, are perspectives highlighted herein. Such studies may drive future efforts towards the rational development of safe and effective technologies to deliver DAP to the skin. Graphical abstract.
氨苯砜（DAP）是一种历史悠久的分子，由于其兼具抗菌和抗炎活性，仍然是各种疾病有前途的治疗药物。然而，其口服应用受到剂量依赖性血液学副作用的限制，这些副作用可能来自全身暴露。为了克服这一限制，过去 20 年来，人们对将 DAP 应用于皮肤的替代方法产生了浓厚的兴趣，特别是在治疗皮肤病方面。在本综述中，介绍了所有提出的用于 DAP 经皮给药的技术策略。大多数报道的研究都致力于含有溶解和微晶药物的凝胶制剂的临床应用和安全性，然而，这种制剂的技术特征仍然缺失。同时，将 DAP 纳入囊泡和颗粒载体（例如纳米和微乳液、非离子囊泡、入侵体、双层囊泡、立方囊泡、固体脂质纳米粒、纳米结构脂质载体、聚合物纳米胶囊和聚合物-脂质-聚合物杂化纳米粒）似乎是提供更好的药物释放控制、增强药物溶解和毛囊靶向的替代方法。事实上，文献中报道的 DAP 局部制剂的主要应用是治疗寻常痤疮，这是一种位于毛囊中的疾病。然而，其他影响皮肤不同区域的疾病（例如红斑狼疮和皮肤利什曼病）也可能受益于含有 DAP 的局部治疗方案。因此，与被动跨膜扩散相比，对附属途径的研究以及药代动力学研究是本文强调的重点。这些研究可能会推动未来的努力，开发安全有效的技术，将 DAP 递送到皮肤。
