A novel concept for the treatment of couperosis based on nanocrystals in combination with solid lipid nanoparticles (SLN)

• Published in: International journal of pharmaceutics Vol. 510; no. 1; pp. 9 - 16
• Main Authors: Pyo, Sung Min, Meinke, Martina, Klein, Anja F., Fischer, Tanja C., Müller, Rainer H.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 20.08.2016
• Subjects: Administration, Cutaneous; Animals; Antioxidant activity; Couperosis treatment; Drug Carriers - administration & dosage; Drug Carriers - metabolism; Drug Therapy, Combination; Humans; Male; Nanocrystals; Nanoparticles - administration & dosage; Nanoparticles - metabolism; Optimized dermal delivery; Penetration profile; Rutin; Rutin - administration & dosage; Rutin - metabolism; Skin Absorption - drug effects; Skin Absorption - physiology; Skin Diseases - drug therapy; Skin Diseases - metabolism; Solid lipid nanoparticles (SLN); Swine; Treatment Outcome; Vitamin A - administration & dosage; Vitamin A - metabolism; Vitamin A1; Vitamin K 1 - administration & dosage; Vitamin K 1 - metabolism; Vitamin K1; Vitamin A1; Solid lipid nanoparticles (SLN); Nanocrystals; Antioxidant activity; Vitamin K1; Penetration profile; Couperosis treatment; Rutin; Optimized dermal delivery; Vitamin A; Vitamin K
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/j.ijpharm.2016.05.017

[Display omitted] For the post laser treatment of couperosis a new dermal formulation was developed combining three actives: vitamin K1, A1 and rutin, where both vitamins were incorporated into solid lipid nanoparticles (SLN) and the poorly soluble antioxidant rutin formulated as nanocrystal. All three formulations were stable over 6 months either on their own or after their incorporation into a hydrogel. Vitamin A1 at 0.3% in emulsions shows local skin irritation due to very rapid release. By forming SLN, prolonged release with less irritation potential but deeper penetration was achieved in porcine ear skin. Due to the nanosized rutin, the new hydrogel showed clearly increased antioxidant activity, representing a stronger protection potential against reactive oxygen species (ROS), compared to marketed anti-redness products with rutin as raw drug powder or water-soluble derivative. In addition, rutin nanocrystals showed up to 5 times pronounced penetration compared to μm-sized raw drug powder. The orientating in-vivo case study revealed a three to six times faster recovery after laser treatment of couperosis by twice daily application of the new hydrogel, regarding scabbed-over areas and erythema. Continued use of the new gel also showed preventive properties against recurrences of veins for at least 8 month.