11:20 - 12:40
Facing the future of cosmetics: the first mitochondria-targeted delivery system for antiaging treatments
Podium 63
Presented by: Natascia Grimaldi
Aimee Vasconcelos, Christian Bellacanzone, Jeremie Nestor, Albert Ginestá, Natascia Grimaldi
Infinitec Activos (Evonik Nutrition & Care), Barcelona
Mitochondria are responsible to produce the 90% of the cell energy, in the form of ATP. While producing energy, mitochondria also generate ROS as by-products. Under homeostatic conditions, mitochondrial ROS (mROS) are neutralized by endogenous antioxidants (i.e. CoQ10). Unfortunately, the more the cells age, the lower is the production of endogenous antioxidants (i.e. CoQ10), the more ROS are accumulated in the mitochondria, causing cells damage and death. CoQ10 is a very powerful biomolecule, having both energizing (ATP production) and antioxidant effects on cells, so supplemented CoQ10 is a perfect ally to counteract cells aging, and in turns skin aging. However, CoQ10 full potential can be only exploited when this is effectively delivered to mitochondria. At Infinitec (Evonik), we have recently developed a cutting-edge delivery system, named Trojan. By the encapsulation of CoQ10 in Trojan, CoQ10 is stabilized in the formula, its skin penetration is enhanced, and its efficacy improved. TrojanQ10 is based on Q10-loaded-PLGA sub-micrometric particles, which surface has been decorated with two peptides. The first peptide is a cell-penetrating peptide (Pentapeptide-4), that can be recognized by fibroblast growth factor receptors and promote TrojanQ10 internalization in fibroblasts. The second peptide, D-Arginyl TyrosinylOrnithinylPhenylalanine, is a mitochondria-penetrating peptide, which sequence has been designed for promoting the preferentially localization of TrojanQ10 at mitochondria level. Once TrojanQ10 reaches the mitochondrial, Q10 is released and can participate to mitochondria respiration, i.e. ATP production and mROS neutralization. A deep physico-chemical characterization of TrojanQ10 has been performed. Particles size and morphology have been determined by DLS and TEM, respectively. TrojanQ10 shows a narrow particles size distribution, with avg. diameter of 300 nm and spherical shape. TrojanQ10 fine structure has been determined by the combination of NMR and XPS, which demonstrated that the two peptides are effectively conjugated to PLGA particles and mainly located on the particles surface. The ability of TrojanQ10 to enhance CoQ10 skin penetration has been assessed on pig-skin, following the OECD 428 guideline. In particular, the penetration of the free active and the encapsulated one have been studied; a faster and more effective penetration has been observed in the case of TrojanQ10. After 2 h, the 60% of the active penetrates the skin and after 6 h, the 90% has already penetrated and reached the dermis. As expected, TrojanQ10 modulate and enhance CoQ10 skin penetration, leading to a deeper and more effective penetration. The selectivity of TrojanQ10 to fibroblasts as well as TrojanQ10 cell trafficking have been also investigated. Fibroblasts have been incubated with TrojanQ10 and the internalization of TrojanQ10 has been studied by Confocal Microscopy. For this study, cells nuclei were stained with DAPI (blue), mitochondria with Mitotracker (green) and TrojanQ10 was labeled with Rhodamine (red). TrojanQ10 first is localized on fibroblast membranes, and then inside the cells. Once in the cytosol, it was possible also to see a preferential localization of TrojanQ10 at mitochondria level. All these results suggested that TrojanQ10 can precisely deliver CoQ10 at mitochondria level. In-vitro efficacy of TrojanQ10 was also assessed by incubating senescent fibroblasts with 0.25% TrojanQ10 and 0.00005% CoQ10 (0.25% TrojanQ10 contains 0.00005% of CoQ10) and measuring the variation of mitochondria membrane potential (directly related to mitochondria activity), ROS and ATP levels. Interestingly, TrojanQ10 showed better activity of CoQ10 in all cases, and in particular TrojanQ10 was able to (i) increase mitochondria membrane potential by 30% (i.e. mitochondria activity), (ii) increase ATP production by a 60%, as well as (iii) reducing ROS levels by 10%. Furthermore, TrojanQ10 increased the synthesis of Collagen IV and VII by a 30%. The in-vivo efficacy of TrojanQ10 as anti-aging was assessed on 18 volunteers (40-60 years old) submitted to a 56-day topical treatment with 1.5% TrojanQ10 (0.0003% of Q10) and 1% Free Q10 (twice per day, in a hemiface protocol). Before and after 56 days of treatment, skin firmness and elasticity were assessed in the crow’s feet area through Cutometer®. TrojanQ10 displayed anti-aging effects, through a significant increase of skin firmness and elasticity, in higher levels than Free Q10. Fine lines were significantly reduced after treatment with TrojanQ10 (- 25% lines area and length). We can conclude that TrojanQ10 changes the game in the delivery of active ingredient to the mitochondria and anti-aging treatment.