Institut Charles Gerhardt Montpellier, UMR 5253 CNRS-ENSCM-UM, Equipe Matériaux Avancés pour la Catalyse et la Santé, 8 rue de l'Ecole Normale, 34296 Montpellier Cedex 5, France.
Institute of Pharmacy, Department of Pharmaceutics, Biopharmaceutics and NutriCosmetics, Free University of Berlin, Kelchstr. 31, Berlin 12169, Germany.
Int J Pharm. 2018 May 5;542(1-2):176-185. doi: 10.1016/j.ijpharm.2018.03.019. Epub 2018 Mar 13.
Quercetin is a flavonoid with strong antioxidant and antiinflammatory activities considered as a potential drug candidate for skin exogenous supplementation. Nevertheless, crude quercetin suffers from poor water solubility and consequently topical inactivity. Therefore, quercetin formulation within a suitable system that overcomes its solubility limitation is a matter of investigation. Three approaches were tested to improve quercetin delivery to skin: liposomes, lipid nanocapsules (LNC) and smartCrystals®. These nanoformulations were compared in terms of average particle size, homogeneity (PDI), quercetin loading and cellular interactions with HaCaT (keratinocytes) and TPH-1 (monocytes) cell lines. Finally, two formulations were selected for testing quercetin delivery to human skin in vivo using stripping test. Different size distribution was obtained with each strategy starting from 26 nm with quercetin LNC, 179 nm with liposomes to 295 nm with quercetin smartCrystals®. The drug loading varied with each formulation from 0.56 mg/ml with liposomes, 10.8 mg/ml with LNC to 14.4 mg/ml with smartCrystals®. No toxicity was observed in HaCaT cells with quercetin and free radical scavenging ability was established at 5 µg/ml. The safety of quercetin at 5 µg/ml was further confirmed on THP-1 cells with efficient free radical scavenging ability. Finally, skin penetration evidenced different behavior between the two selected forms (LNC and SmartCrystals®), which could lead to different promising strategies for skin protection. On one side, quercetin smartCrystals® seems to enable the superficial deposition of quercetin on top of the skin, which presents a good strategy for a quercetin-based sunscreen product. On the other side, LNC seems to allow quercetin delivery to viable epidermis that holds the promise for skin inflammatory disorders such as psoriasis.
槲皮素是一种具有强抗氧化和抗炎活性的类黄酮，被认为是一种有潜力的皮肤外源性补充药物候选物。然而，原槲皮素的水溶性较差，因此局部活性较低。因此，将槲皮素制成合适的系统制剂以克服其溶解度限制是一个研究课题。为了提高槲皮素向皮肤的递送，我们测试了三种方法：脂质体、纳米脂质体（LNC）和智能晶体®。从平均粒径、均匀性（PDI）、槲皮素载药量和与 HaCaT（角质形成细胞）和 TPH-1（单核细胞）细胞系的细胞相互作用等方面比较了这些纳米制剂。最后，选择了两种制剂进行体内人体皮肤的递送测试，采用剥落试验。从 LNC 的 26nm、脂质体的 179nm 到 smartCrystals®的 295nm，每种策略都获得了不同的粒径分布。每种制剂的载药量也不同，从脂质体的 0.56mg/ml、LNC 的 10.8mg/ml 到 smartCrystals®的 14.4mg/ml。在 HaCaT 细胞中，槲皮素无毒性，自由基清除能力在 5µg/ml 时得到证实。在 THP-1 细胞中，5µg/ml 的槲皮素的安全性进一步得到证实，具有有效的自由基清除能力。最后，皮肤渗透证明了两种选定形式（LNC 和 SmartCrystals®）之间的不同行为，这可能为皮肤保护提供不同的有前途的策略。一方面，槲皮素 smartCrystals®似乎可以使槲皮素在皮肤表面沉积，这是一种基于槲皮素的防晒霜产品的良好策略。另一方面，LNC 似乎可以使槲皮素递送到有活力的表皮，这为治疗银屑病等皮肤炎症性疾病提供了希望。
