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.
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.
Int J Pharm. 2017 Feb 25;518(1-2):167-176. doi: 10.1016/j.ijpharm.2016.12.043. Epub 2016 Dec 21.
Quercetin is a plant flavonoid with strong antioxidant and antiinflammatory properties interesting for skin protection. However, its poor water solubility limits its penetration and so its efficiency on skin. For this purpose, quercetin lipid nanocapsules were formulated implementing phase inversion technique wherein several modifications were introduced to enhance quercetin loading. Quercetin lipid nanocapsules were formulated with two particle size range, (50nm and 20nm) allowing a drug loading of 18.6 and 32mM respectively. The successful encapsulation of quercetin within lipid nanocapsules increased its apparent water solubility by more than 5000 fold (from 0.5μg/ml to about 5mg/ml). The physicochemical properties of these formulations such as surface charge, stability and morphology were characterized. Lipid nanocapsules had spherical shape and were stable for 28days at 25°C. Quercetin release from lipid nanocapsules was studied and revealed a prolonged release kinetics during 24h. Using DPPH assay, we demonstrated that the formulation process of lipid nanocapsules did not modify the antioxidant activity of quercetin in vitro (92.3%). With the goal of a future dermal application, quercetin lipid nanocapsules were applied to THP-1 monocytes and proved the cellular safety of the formulation up to 2μg/ml of quercetin. Finally, formulated quercetin was as efficient as the crude form in the protection of THP-1 cells from oxidative stress by exogenous hydrogen peroxide. With its lipophilic nature and occlusive effect on skin, lipid nanocapsules present a promising strategy to deliver quercetin to skin tissue and can be of value for other poorly water soluble drug candidates.
槲皮素是一种具有强抗氧化和抗炎特性的植物类黄酮，对皮肤保护很有意义。然而，其较差的水溶性限制了其在皮肤中的渗透和效率。为此，采用相转化技术制备了槲皮素脂质纳米囊，其中引入了几种修饰方法来提高槲皮素的载药量。制备了两种粒径范围的槲皮素脂质纳米囊（50nm 和 20nm），分别可以实现 18.6 和 32mM 的药物载药量。将槲皮素成功包封在脂质纳米囊中，使其表观溶解度提高了 5000 多倍（从 0.5μg/ml 提高到约 5mg/ml）。对这些制剂的物理化学性质，如表面电荷、稳定性和形态进行了表征。脂质纳米囊呈球形，在 25°C 下稳定 28 天。研究了脂质纳米囊的槲皮素释放，发现其在 24 小时内呈现出延长的释放动力学。通过 DPPH 测定，我们证明了脂质纳米囊的制剂过程没有改变槲皮素在体外的抗氧化活性（92.3%）。为了实现未来的皮肤应用，将槲皮素脂质纳米囊应用于 THP-1 单核细胞，证明了该制剂在 2μg/ml 槲皮素浓度下对细胞的安全性。最后，研究表明，与粗制形式相比，制剂形式的槲皮素在保护 THP-1 细胞免受外源性过氧化氢引起的氧化应激方面同样有效。由于其亲脂性和对皮肤的封闭作用，脂质纳米囊为将槲皮素递送到皮肤组织提供了一种有前途的策略，并可能对其他水溶性差的候选药物有价值。
