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Full Paper in PDF Format The Study for Pterostibene Stability using Adaptable Vesicle Ji Hong Geun, Cho Se Hee , Kim Jeong Dong, Yu Hyo Gyoung 1 Jang Hye In 2 (1) H&A PharmaChem, R&D center, Bucheon-city, 421-837,Korea (2) Dep of oriental Medical and Herbal Cosmetic Science, Semyung University Objective: Pterostilbene is a stilbenoid chemically related to resveratrol . It is thought to be the key compound found predominantly in blueberries (as well as grapes ) that exhibit anti- cancer , anti-hypercholesterolemia , anti-hypertriglyceridemia properties, as well as fight off and reverse cognitive decline. It is believed that the compound also has anti- diabetic properties, but so far very little has been studied on this issue. Additionally, it is also touted as a potent anti-fungal. In these several years, as many people have been attracted by the functional cosmetics, there have been a lot of study to enhance the stability of active ingredients for light, heat, oxygen, etc. in the academic and industrial field. Especially, Pterostilbene is a powerful ingredient to reduce wrinkles, but its stability depends on environmental factors such as solvent, temperature, oxygen and light. Introduction A recent development in cosmetics has been the pursuit of high functionality. However, it is a common feature that the raw materials of functionality are unstable for light, heat and oxygen. Therefore, new technology of stabilization for functional raw material has been required. An inducible antifungal compound in grapevine leaves ( Vitis vinifera L., cv Cabernet-Sauvignon) has been identified as trans -pterostilbene (3,5-dimethoxy-4′- hydroxy stilbene). It is only a minor component of the phytoalexin response of V. vinifera but its antifungal activity is relatively high by comparison with resveratrol and the viniferins, stress metabolites which have been identified previously in grapevine. Resveratrol, a stilbenoid antioxidant found in grapes, wine, peanuts and other berries, has been reported to have hypolipidemic properties. We investigated whether resveratrol and its three analogues (pterostilbene, piceatannol, and resveratrol trimethyl ether) would activate the peroxisome proliferator-activated receptor α (PPARα) isoform. This nuclear receptor is proposed to mediate the activity of lipid- lowering drugs such as the fibrates. Inhibition of cancer growth by resveratrol ( trans -3,5,4′-trihydroxystilbene; RESV), a phytoalexin present in many plant species, is limited by its low bioavailability. Pterostilbene (3,5-dimethoxy-4′-hydroxystilbene; PTER) and quercetin (3,3′,4′,5,6- pentahydroxyflavone; QUER), two structurally related and naturally occurring small polyphenols, show longer half-life in vivo. In vitro growth of highly malignant B16 melanoma F10 cells (B16M-F10) is inhibited (56%) by short-time exposure (60 min/day) to PTER (40 µM) and QUER (20 µM) (approximate mean values of plasma concentrations measured within the first hour after intravenous administration of 20 mg/kg of each polyphenol). Intravenous administration of PTER and QUER (20 mg/kg per day) to mice inhibits (73%) metastatic growth of B16M-F10 cells in the liver, a common site for metastasis development. In these several years, as many people have been attracted by the functional cosmetics, there have been a lot of study to enhance the stability of active ingredients for light, heat, oxygen, etc. in the academic and industrial field. Especially, Pterostilbene is a powerful ingredient to reduce wrinkles, but its stability depends on environmental factors such as solvent, temperature, oxygen and light. Materials and methods In this study, the stability and skin penetration of Pterostilbene are improved by adaptable vesicle system(AV). We prepared AV(20-100nm) using Lysolecithin/ Polyglycerin ester/ Phospholipid /Chocolate/ Pterostilbene system with microfluidizer . Results: According to chromameter date, the color stability of AV system was enhanced by 3 ~ 5 times compared with Pterostilbene raw materials. We also confirmed through HPLC analysis that Pterostilbene in our system is more long lasting. The effect of skin penetration was improved, too. Identification of AV Formation TEM(transmission electron microscopy) are used to identify the formation of liposome. As shown in fig. 1, it is seen that nano-emulsion and liposome are well formed by AV give them more stability. Particle Size Distribution We also studied for particle size distribution of liposome with laser light scattering system. AV has the size distribution from 20 to 200 nm and mean diameter about 74.4 nm. (Fig.2.) Livability of Pterostilbene Let’s see the content change under light exposure first. In general liposome system, after 30 days, Pterostilbene content remained was about 35 percent. In our system, its content was about 80%. Under 40 ℃, Pterostilbene content in general liposome was decreased to about 55% and about 90%, in ours. Under 25 ℃, in general liposome, about 90% and about 95% in ours. The reason for enhanced livability is also attributed to AV system. Skin Penetration Effect Skin penetration effect was enhanced by almost 60 %. If we consider only the particle size of liposome, general liposome having more smaller particle size should have good penetration rate compared with AV system. But in our system, important thing is actually penetrated materials are primary liposomes having similar size with general liposomes, not whole AV system. Therefore, when AV system is in contact with skin especially stratum corneum, primary liposomes in only outmost layer of AV system, not all liposomes, are released and pass through. In next stage, primary liposomes in new outmost layer are released and pass through. This kind process is repeated. So unlike general liposome, Pterostilbene in AV system is not released all at once. That means Pterostilbene is slowly and steady released from outmost lamellar layer to inmost lamella. Therefore, penetration efficiency is enhanced due to AV.(Fig.3.) Results: According to chromameter date, the color stability of AVsystem was enhanced by 3 ~ 5 times compared with Pterostilbene raw materials. We also confirmed through HPLC analysis that Pterostilbene in our system is more long lasting. The effect of skin penetration was improved, too. Conclusions: The skin adsorption and bio-availability can be improved by the only general liposome, which is composed of phospholipid etc., but the general liposome is relatively unstable. In order to better this unstability, we used adaptable vesicle system(AV) that capsulated Pterostilbene . AV System was 20 through 200 nm. Mean diameter was 74.4nm. Our system was more stable than general liposome. Figure.1 Microphotograhs of AV. Figure.2. Particle size distribution of AV. Skin Penetration 0.40 0.351 0.35 0.30 0.25 0.20 0.15 0.102 0.10 Penetration rate(%) Penetration 0.05 0.00 General Liposome AV Figure.3. Skin penetration effect of AV .
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