Petrovici Andreea-Georgiana, Spennato Mariachiara, Bîtcan Ioan, Péter Francisc, Cotarcă Livius, Todea Anamaria, Ordodi Valentin Laurențiu
Biocatalysis and Green Chemistry Group, Faculty Chemical Engineering, Biotechnologies and Environmental Protection, University Politehnica Timisoara, Vasile Pârvan 6, 300223 Timisoara, Romania.
Department of Civil, Chemical, Environmental and Materials Engineering, Alma Mater Studiorum University of Bologna, 40126 Bologna, Italy.
Pharmaceuticals (Basel). 2025 Aug 26;18(9):1273. doi: 10.3390/ph18091273.
Azelaic acid (AzA), a saturated dicarboxylic acid, is indicated for the treatment of acne vulgaris, rosacea, melasma, and post-inflammatory hyperpigmentation. Its antimicrobial, anti-inflammatory, and antimelanogenic properties support its use; however, its poor aqueous solubility and limited skin permeability constrain its optimal topical delivery. This review summarizes clinical evidence and advances in formulations-including conventional vehicles, polymeric/lipid nanocarriers, and deep eutectic solvent (DES) systems-to promote more effective and well-tolerated use. Across indications, 15-20% azelaic acid (AzA) formulations produced clinically meaningful improvements with mild, transient local irritation. For acne vulgaris, reductions in inflammatory and noninflammatory lesions were comparable to those of topical retinoids/adapalene, and tolerability was superior in some studies. For rosacea, the 15% gel formulation was comparable to metronidazole in reducing papules, pustules, and erythema while maintaining negligible systemic exposure. In melasma and other dyschromias, 20% cream demonstrated efficacy similar to hydroquinone, exhibiting a favorable safety profile. Advanced delivery systems, including liposomes, niosomes/ethosomes, nanostructured lipid carriers, microemulsions, nanosponges, and DES platforms, increased AzA solubilization, cutaneous deposition, and stability. This enabled dose-sparing strategies and improved adherence. Data on AzA cocrystals and ionic salts suggest additional control over release and irritation. AzA remains a versatile and well-tolerated dermatologic agent whose performance is strongly vehicle-dependent. Rational selection and engineering of carriers, particularly DES-integrated polymeric and lipid systems, can mitigate solubility and permeability limitations, enhance skin targeting, and reduce irritation in the treatment of acne and rosacea.
壬二酸（AzA）是一种饱和二元羧酸，适用于治疗寻常痤疮、玫瑰痤疮、黄褐斑和炎症后色素沉着。其抗菌、抗炎和抗黑素生成特性支持其应用；然而，其较差的水溶性和有限的皮肤渗透性限制了其最佳局部给药。本综述总结了临床证据以及制剂方面的进展，包括传统载体、聚合物/脂质纳米载体和低共熔溶剂（DES）系统，以促进更有效且耐受性良好的使用。在各种适应症中，15 - 20%的壬二酸（AzA）制剂产生了具有临床意义的改善，伴有轻度、短暂的局部刺激。对于寻常痤疮，炎症性和非炎症性皮损的减少与局部维甲酸/阿达帕林相当，并且在一些研究中耐受性更佳。对于玫瑰痤疮，15%的凝胶制剂在减少丘疹、脓疱和红斑方面与甲硝唑相当，同时全身暴露可忽略不计。在黄褐斑和其他色素沉着异常中，20%的乳膏显示出与氢醌相似的疗效，安全性良好。先进的给药系统，包括脂质体、非离子表面活性剂囊泡/醇质体、纳米结构脂质载体、微乳、纳米海绵和DES平台，提高了AzA的溶解度、皮肤沉积和稳定性。这使得能够采用节省剂量的策略并提高依从性。关于AzA共晶和离子盐的数据表明对释放和刺激有额外的控制作用。AzA仍然是一种用途广泛且耐受性良好的皮肤科药物，其性能强烈依赖于载体。合理选择和设计载体，特别是DES整合的聚合物和脂质系统，可以减轻溶解度和渗透性限制，增强皮肤靶向性，并减少痤疮和玫瑰痤疮治疗中的刺激。
