Hatahet T, Morille M, Hommoss A, Dorandeu C, Müller R H, Bégu S
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.
Eur J Pharm Biopharm. 2016 May;102:51-63. doi: 10.1016/j.ejpb.2016.03.004. Epub 2016 Mar 4.
Flavonoids are natural plant pigments, which possess high antioxidative and antiradical activities. However, their poor water solubility led to a limited bioavailability. To overcome this major hurdle, quercetin nanocrystals were produced implementing smartCrystals® technology. This process combines bead milling and subsequent high-pressure homogenization at relatively low pressure (300bar). To test the possibility to develop a dermal formulation from quercetin smartCrystals®, quercetin nanosuspensions were admixed to Lutrol® F127 and hydroxythylcellulose nonionic gels. The physicochemical properties (morphology, size and charge), saturation solubility, dissolution velocity and the antioxidant properties (DPPH assay) as well as the cellular interaction of the produced quercetin smartCrystals® were studied and compared to crude quercetin powder. Quercetin smartCrystals® showed a strong increase in the saturation solubility and the dissolution velocity (7.6 fold). SmartCrystals® loaded or not into gels proved to be physically stable over a period of three months at 25°C. Interestingly, in vitro DPPH assay confirmed the preservation of quercetin antioxidative properties after nanonization. In parallel, the nanocrystalline form did not display cellular toxicity, even at high concentration (50μg/ml), as assayed on an epithelial cell line (VERO cells). In addition, the nanocrystalline form confirmed a protective activity for VERO cells against hydrogen peroxide induced toxicity in vitro. This new formulation presents a promising approach to deliver quercetin efficiently to skin in well-tolerated formulations.
黄酮类化合物是天然植物色素，具有高抗氧化和抗自由基活性。然而，它们较差的水溶性导致生物利用度有限。为克服这一主要障碍，采用smartCrystals®技术制备了槲皮素纳米晶体。该过程结合了珠磨和随后在相对低压（300巴）下的高压均质化。为测试由槲皮素smartCrystals®开发皮肤制剂的可能性，将槲皮素纳米悬浮液与Lutrol® F127和羟乙基纤维素非离子凝胶混合。研究了所制备的槲皮素smartCrystals®的物理化学性质（形态、尺寸和电荷）、饱和溶解度、溶解速度和抗氧化性能（DPPH测定）以及细胞相互作用，并与粗槲皮素粉末进行比较。槲皮素smartCrystals®的饱和溶解度和溶解速度显著增加（7.6倍）。装入或未装入凝胶的SmartCrystals®在25°C下三个月内物理稳定。有趣的是，体外DPPH测定证实了纳米化后槲皮素抗氧化性能的保留。同时，即使在高浓度（50μg/ml）下，纳米晶形式在一种上皮细胞系（VERO细胞）上测定时也未显示细胞毒性。此外，纳米晶形式证实了对VERO细胞在体外针对过氧化氢诱导的毒性具有保护活性。这种新制剂为以耐受性良好的制剂将槲皮素有效递送至皮肤提供了一种有前景的方法。
