Tomorrow s vision...today! Delivery Systems: Liposomes
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1 Tomorrow s vision...today! Delivery Systems: Liposomes
2 Introduction Active Concepts has built itself upon three pillars; innovative technology platforms, market leading customer support, and products with a purpose. We have diligently embarked on a quest to develop complex, active ingredients with technologies that allow formulators to make desired, sought after claims to meet the ever changing market demand for new claims. With almost two decades of experience creating active ingredients, a reoccurring question is often how to effectively maximize the delivery to the skin. After in-depth research on delivery systems, Active Concepts recommends delivery via liposomes for enhanced penetration. Skin, being the human body s largest organ, is the first line of defense against the external environment. Active ingredients affect the skin through a multitude of mechanisms to either deliver or propagate the specific desired result. Extensive research has been conducted to determine how to deliver actives through the stratum corneum to varying depths of the skin. One conclusion of this research has shown the preferred mechanism for delivering active ingredients into the skin is by the way of liposome incorporation. Liposomes are microscopic spherical, self-enclosed capsules in which a phospholipid bilayer sequesters hydrophilic materials. The phospholipid bilayer orients based on the the polar head region assembling towards the aqueous phase, while the nonpolar tail orientates towards the inside of the sphere. This system allows for encapsulation of both lipophilic and hydrophilic components. The hydrophilic exterior of the bilayer protects the incorporated components from degradation while also enhancing the delivery of the actives into the skin. In addition, the vesicular structure liposomes exhibit mimic that of the skin s own natural stratum corneum. This flexible vesicular structure coupled with the amphiphilic nature of phospholipids creates a transdermal vehicle to deliver the encapsulated materials to the preferred destination.
3 Lip o some / lipә,sōm or līpә,sōm/ Noun/Biochemistry highly organized minute spherical structures, consisting of concentric bilayered vesicles in which an aqueous volume is entirely enclosed by a membraneous lipid bilayer 1 Liposomes were first described by Dr. Alec D. Bangham in 1961 at Braham Institute in Cambridge. While testing the institute s new electron microscope, negative stain added to dry phospholipids provided the first real evidence that the cell membrane was a bilayer lipid structure. 1 Liposomes were then designed as artificial cell models to study cell membranes and interactions. Since then, vast amounts of research have detailed liposome mechanisms in drug delivery, personal care, and even in food. Dior Science first introduced the use of liposomes in cosmetics in 1986 within the well-known range Capture. 2 Marketed as containing a Liposome Complex which claimed to effectively convey active ingredients into the skin within in microcapsules 300 times smaller than a normal cell was the consumer s first glimpse at liposomes in action. 3 The structure and amphiphilic nature allows the liposomes to penetrate the epidermal barrier and travel deeper than free materials to deliver the anticipated results. A study was published in the DovePress on Clinical, Cosmetic, and Investigation Dermatology titled Phosphatidylcholine liposomes as carriers to improve topical ascorbic acid treatment of skin disorders analyzed liposomes and human skin penetration via Franz cells. When non-encapsulated materials are placed on the skin a range of factors determine the fate of the material. Stability, solubility, lipophilicity, and size are all obstacles the active must overcome the epidermal barrier. Liposomes, which resemble the basic structures of cellular membranes, create a more beneficial interaction with skin cells.
4 The Science From this study, Figure 1 illustrates the penetration of empty phosphatidylcholine liposomes into human whole abdomen skin preparations mounted on Franz cells. The Franz cells were exposed to the empty phosphatidylcholine liposomes and photos were taken at 0 hours, 48 hours, and 72 hours. Oil red staining skin histology was performed to label lipids from liposomes in different skin layers. 4 It is visually apparent that the liposomes penetrated through the epidermis to the dermis both after 48 hours and after 72 hours compared to the control. Fluorescein liposomes were added to the surface of whole human skin at different times followed by a surface skin wash and visualization of skin fluorescein penetration by fluorescence microscopy. 4 Figure 1. Control, 48 hour, and 72 hour photo depicting penetration of empty phosphatidylcholine liposomes into human whole abdomen skin preparations mounted on Franz Cells. Within the same original research study, fluorescein, a lipophilic fluorescence substance, was used to monitor and quantify liposomal penetration through different layers of whole human abdomen skin. Figure 2. Liposome encapsulate fluorescein penetration vs. free form fluorescein penetration. It was concluded that fluorescein liposomes reached the epidermis after three hours of exposure and that their content, fluorescein in the free form in receptor medium of Franz cells, started reaching the dermis progressively after 20 hours which can be visualized in Figure 2. 4
5 The evolution of liposomes is one of the most important advancements in skin care delivery systems. -Executive Director, Product Development at Clinique Liposomes proven delivery system yields a multitude of benefits; enhancing the penetration of actives yielding increased efficacy, offering time release mechanisms, protecting and delivering otherwise unstable ingredients, and opening the door to the ability to target specific cells. Liposomes can differ in size with a range in diameter between nm, and they can be found in unilamellar and multilamellar forms. While multilamellar structures are great for specific tasks, they are not stable as raw materials or in formulations. Unilamellar vesicles are small, exceptionally stable molecules offering high stability for the incorporation into personal care products. Liposome Effective Transport across a barrier Allows for targeted product development Can increase product stability and efficacy Active Concepts produces a variety of unilamellar vesicles employing a proprietary composition of phospholipids utilizing high shear techniques. These specifically created vesicles have a greater Zeta Potential than typical liposomes. Zeta Potential is the measure of the electrostatic or charge repulsion between particles. The magnitude of the Zeta Potential is indicative of the colloidal stability, a larger Zeta Potential yields higher degrees of stability. In an effort to bring this stable delivery system to our customers, Active Concepts offers many standard liposomes. The most popular standard liposomes are outlined within the following pages. Free Material Unable to penetrate across a barrier Non-specific product efficacy Decreased stability in-vivo, less effective
6 Active Concepts Offerings Active Concepts offers many standard liposomes. Below the most popular are listed. Product Code & Name INCI Name Function 60104PF AC Vitamin ACE Water & Phospholipids & Tocopheryl Acetate & Retinyl Palmitate & Ascorbyl Palmitate Utilizes antioxidant protection from essential vitamins A, C, & E drastically preventing the oxidation process to help maintain healthy cells AC Azelaic Acid Liposome 60134PF AC Unloaded 60124PF AC Retinol 60131PF AC Caffeine 60155SH AC EGF Liposome SH 60155PF AC EGF AC Cinnamon Liposome Water & Butylene Glycol & Azelaic Acid & Lecithin & Xanthan Gum & Atelocollagen & Sodium Chondroitin Sulfate Water & Phospholipids Water & Phospholipids & Retinol Water & Phospholipids & Caffeine Water & Phospholipids & sh- Oligopeptide-1 Water & Phospholipids & rh- Oligopeptide-1 Water & Cinnamomum Cassia Bark Extract & Phospholipids Offers anti-inflammatory, anti bacterial, anti-acne benefits by regulating the production of keratinocytes. Unloaded delivery system. Harnesses the well known benefits of retinol and is recommended for the delivery of age-defying and antioxidant benefits. Caffeine increases microcirculation, delivering slimming and de-puffing benefits while helping to reduce swelling which can cause aging effects. Encapsulated biotechnologically derived Epidermal Growth Factor produced from recombinant DNA promotes collagen production, reduces fine lines, conditions, and evens skin tone. Encapsulated, biotechnologically derived via E. coli Epidermal Growth Factor. Perhaps one of the best understood signaling pathways in the human body, EGFR promotes collagen production, reduces fine lines, conditions, and evens skin tone. Effectively delivers antioxidants to the skin while sequestering copper to down-regulate tyrosinase activity to lighten and even skin tone while allowing the skin to readily absorb potent antioxidant properties.
7 Active Concepts Offerings Active Concepts offers many standard liposomes. Below the most popular are listed. Product Code & Name INCI Name Function 60146PF AC Co-Enzyme Q 10 Water & Phospholipids & Ubiquinone Neutralizes harmful free radicals that are one of the major causes of aging PF AC Salicylic Acid Parameter Storage Formulation Temperature Interactions Water & Salicylic Acid & Phospholipids Active Concepts offers many standard liposomes which are listed above. However, the liposome market is dominated by custom developed liposomes to provide targeted delivery, enhanced efficacy, and a tailored consumer experience. Considering customized, liposomal product development allows formulators to create brand differentiating products and ensure optimal active delivery... a truly Active Concept. Contact your Active Concepts regional sales representative to discuss your liposome custom development needs. Guidelines Store in cool, dry place at room temperature. Do not expose to excess heat or cold C Ideal in aqueous or O/W systems Surfactant system, add after system is structured. Designed to enhance the delivery of salicylic acid to provide potent benefits in addition to improving its solubility, allowing for the creation of products with a luxurious and elegant feel.
8 References: 1-Deamer, David. From Banghasomes to liposomes: A memoir of Alec Bangham, The FASEB Journal. vol. 24 no May Dior Science. Dior. N.p., n.d. Web. 22 Aug Dior Captures Essence for a Youthful Look. New Straits Times [Malaysia] 15 Jan.1998: Print. 4-Milara, Javier, Gabriel Serrano, Patricia Almudever, Juan-Manuel Serrano, Ana Torrens, Inmaculada Expósito, and Julio Cor ijo. Phosphatidylcholine Liposomes as Carriers to Improve Topical Ascorbic Acid Treatment of Skin Disorders. CCID Clinical, Cosmetic and Investigational Dermatology (2015): 591. Dove Press. Web. 2 Aug Gaspar U. M. M. Bakowsky, and C. Ehrhardt Inhaled Liposomes Current Strategies and Future Challenges vol no 3 p. 2008;4:1-13. Tomorrow s vision...today! Active Concepts, LLC Lincolnton, NC. USA www. activeconceptsllc.com Office: +1 (704) info@activeconceptsllc.com Active Concepts S.r.l. Milano ITALY Tel info@activeconcepts.it Active Concepts LLC, Asia Kaohsiung, Taiwan Tel josephyeh@activeconceptsllc.com
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