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Jar Deconstructed: Liposomes

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Liposomes are tiny delivery vehicles that transport ingredients into the skin. Made from lipids, liposomes simulate skin’s structure to more easily pass through or manipulate the skin barrier to deliver their contents. While initially believed to penetrate intact into skin, traditional liposomes have more recently been shown to instead act like penetration enhancers, bonding with outer lipid layers of the stratum corneum and bursting, allowing contents to enter skin.1-3

Other types of delivery vehicles, including elastosomes, nano-vesicle carriers, liposome-like structures, lamellar nano-vesicles, niosomes, etiosomes, Transfersomesa, glycerosomes, hyalurosomes, etc.,4 vary in design and act via different mechanisms, giving them different levels of efficacy. Transfersomes, for example, incorporate a surfactant, which gives them elastic properties so they can deform and pass between the cells of the skin barrier, arriving intact in the epidermis.5

Recent work out of India has attempted to optimize Transfersomes containing epigallocatechin gallate (EGCG) and hyaluronic acid to combine the UV-protective benefits of both compounds and impart antioxidant and anti-aging effects in skin. Initial results are promising.6

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This column will review new research and applications for liposomes, which are well-known and prevalent in today’s skin care products. But to understand their applications, it is first helpful to know some fundamentals about how they work.

Liposomes in Action

According to Polla, liposomes can carry hydrophilic (water-loving) substances and/or lipophilic (lipid-, oil- or fat-loving) substances. Liposomes penetrate the skin via five main mechanisms and a sixth peripheral route.5

  1. They can penetrate independently to release their active substances; some controversies over this route exist.
  2. They may also absorb then fuse with the skin’s constituents, changing the structure of intercellular regions and increasing the permeability of skin. This enhances the penetration of the encapsulated molecules.
  3. Liposomes can also gravitate to the skin surface, where encapsulated molecules directly transfer to the skin.
  4. They can fuse and mix within the lipid matrix of the skin, increasing the distribution of molecules therein.
  5. Some liposomes, e.g., Transfersomes and deformable liposomes, appear to penetrate fully intact into skin.
  6. Peripherally, liposomes can also penetrate skin through cutaneous annexes such as hair follicles.

Attacking Acne

A study from the Catholic University of Korea describes erythromycin-loaded liposomes for combined antibacterial and skin disorder therapies. These were designed to be activated by the enzyme lipase since inflammation-inducing Propionibacterium acnes (P. acnes) secrete lipase. So, in the presence of P. acnes and their lipases, the erythromycin is liberated and provides antibacterial effects.7

In relation, work from The Arctic University of Norway showed how benzoyl peroxide and the antibiotic chloramphenicol could be encapsulated together in liposomes to achieve synergistic effects against conditions such as acne.8

A State of Repair

Research from Seoul explored how liposomes containing epidermal growth factors (EGFs) and hyaluronic acid (HA) could aid in the treatment of wounds. Before encapsulation, combinations of EGFs and other materials, some including HA, were developed. These imparted synergistic effects for fibroblast proliferation and collagen synthesis.9 Next, these combinations were incorporated into cationic elastic liposomes (ELs) and in test models, liposomes with HA showed 23% higher wound recovery. Furthermore, ELs containing HA accelerated wound closure in a diabetic mouse model.

While it may come as no surprise that HA-complexed blends synergistically enhanced healing, the significance of this work is that liposomes could deliver growth factors, since they are limited by low percutaneous absorption. Furthermore, different GFs could be delivered appropriately for the different stages of healing.9

Beneath growth factors themselves lies the extracellular matrix (ECM) of skin, which is well-known to provide structural support to surrounding cells. Interestingly, a patent application from the Sogang University Research Foundation describes a liposome capable of promoting cell attachment and growth by delivering ECM itself to cells. This suggests applications for skin repair, skin rejuvenation therapies, etc.10

Antioxidant Ultimatum

Finally, coenzyme Q10 (CoQ10) is an old favorite for skin, as this lipid-soluble antioxidant is essential for electron transport and energy generation in mitochondria. In relation, D-panthenyl triacetate (PTA), an oil-soluble derivative of D-panthenol, is essential for coenzyme A synthesis in skin, helping to manage the negative effects of oxidative stress such as skin redness, fine lines and roughness.

Researchers in Istanbul attempted to put the two together in liposomal formulas to increase ingredient stability and skin penetration.11 They found that the release of the optimized blends could be controlled from the liposomes, which also remained stable in storage at 4°C for at least 60 days. Liposomes are therefore a promising delivery system for both CoQ10 and PTA in various topical applications.

In the Spa

In the spa industry, liposomes are frequently utilized to deliver key actives, with hyaluronic acid winning the award for most popular and hydration often the name of the game.

Rhonda Allison uses a liposome complex in its C Stem Cell Skin Strengthener to deliver hyaluronic acid for lasting hydration. A hyaluronic acid complex comprised of three moisturizing compounds is incorporated into a liposome complex of sphingolipids, phospholipids and honey to restore the lipid barrier of the horny layer in the epidermis and increase water absorbtion in the corneocytes to form a hydrating film for lipid barrier repair and lasting hydration.

“[Our liposome complex] focuses on all the facets of moisturizing the cells as well as creating a delivery system for the other components in the formula to go deeper into the layers of the skin. This complex provides lipid, NMF and TEWL support, which is so key for a healthy stratum corneum while delivering powerful vitamin C and antioxidants to the skin,” noted Shannon Esau, director of education for Rhonda Allison.

Hyaluronic acid is also encapsulated in a new generation of liposomes called Sphérulites in Pevonia’s C Evolutive Eye Gel. These liposomes are time-released, carrying active ingredients between the multishield, multi-lamellae structure. The hyaluronic acid contained in the Sphérulites releases moisture throughout the day.

“Sphérulites are advanced multi-lamellae active agent carriers made of soy lecithin, which feature progressive 12-hour time-release delivery of the encapsulated contents and possess long lasting structural stability. Sphérulites are small enough to penetrate intercellular spaces and carry intact ingredients to specific target areas preventing their early degradation and empowering performance. In [this eye product], sphérulites encapsulate, protect and time deliver hyaluronic acid for consistent and ongoing hydration of the delicate eye contour area for a youthful appearance.” added Christian Jurist, M.D., global education director at Pevonia.

Le Mieux employs encapsulated liposomes that transport both hyaluronic acid and multiple active ingredients into targeted sites. Le Mieux Hydra Bio Technology is a patented complex of ingredients that are double-encapsulated and micro-sized in a liposomal hydrophilic and lipophilic carriers, ensuring timely release and optimum delivery for phenomenal anti-aging solutions.

“Liposomes are among the best known and widely used vesicles in delivery systems for skin care formulations. First used in drug delivery systems, liposomes have become popular in the anti-aging cosmetics industry because they can enhance the performance of skin care formulations due to their success in being absorbed into the skin. The submicroscopic microspheres have diameters ranging between 25 and 5000 nanometers and are used for delivering vitamins, botanicals, marine lipid extracts, ascorbyl palmitate, tocopherol, retinol, coenzyme Q10, niacinamide, hyaluronic acid, and other active cosmetic ingredients into the skin,” explained Janel Luu, founder Le Mieux and PurErb.

Guinot uses what it terms hydro-liposomes to deliver moisture to skin in its Hydrazone moisturizer. Rather than active, hydro-liposomes are filled with water, which is diffused into the epidermis to quench dehydrated skin. It is said to bind water in the skin durably for continuous moisture throughout the day.

Liposomes also deliver lasting moisturization in Glymed’s Photo-Age Environmental Protection Gel 15. In it, liposomes deliver essential moisture to the skin.

Finally, Osmosis coats its ingredients with a liposome called phosphatidylcholine to deliver them deeper into the skin. The delivery technology is said to improve product penetration by 600%. This liposome shares the same properties with all of our ‘coated’ cells. When used to coat ingredients, it naturally enhances penetration into the cell as well as protects it during the liposome delivery.

“Not all liposomes are the same. Using phosphatidylcholine (PC) can help a product, but it does not naturally produce effective liposomes. [Here] 95% pure PC is combined with a specially designed “fluidizer” that compresses the PC around the ingredients with high pressures. Research shows it increases penetration of ingredients by 600% on average. Many ingredient, like retinols, are larger and average 2% penetration. PC makes the ingredients bioavailable since PC is what our cell walls are made of. It also has been shown to protect from UVB damage, increase moisture, reduce oil and more,” added Ben Johnson, M.D.founder of Osmosis.

Conclusions

Liposome delivery has long been established for skin care, although today’s solutions show unprecedented shifts in format and function. Ingredients must be delivered on demand, in unforeseen scenarios and loaded with next-generation visions for the future.

REFERENCES

    1. www.cosmeticsandtoiletries.com/research/patents/Not-to-Burst-Your-Liposome-Bubble-378316781.html
    2. https://link.springer.com/protocol/10.1007/978-1-4939-6591-5_9
    3. www.sciencedirect.com/science/article/pii/0168365992902119
    4. www.cosmeticsandtoiletries.com/research/patents/Patent-Pick-Nano-bio-vesicles-Break-the-Skin-Barrier-381644841.html
    5. www.cosmeticsandtoiletries.com/research/biology/premium-Penetration-of-Cosmetics-Into-and-Through-the-Stratum-Corneum-201254021.html
    6. www.tandfonline.com/doi/abs/10.1080/10717544.2016.1228718
    7. www.sciencedirect.com/science/article/pii/S0142961217304593
    8. www.sciencedirect.com/science/article/pii/S0928098716305103
    9. www.sciencedirect.com/science/article/pii/S1742706117302805
    10. www.cosmeticsandtoiletries.com/research/patents/Patent-Pick-Liposomes-Deliver-Next-gen-Cell-Regeneration-415591083.html
    11. www.ncbi.nlm.nih.gov/pmc/articles/PMC5511013/

(All websites accessed Nov 9, 2017)

aTransfersome is a trademark of IDEA AG.

Rachel Grabenhofer is the managing editor of Cosmetics & Toiletries, Skin Inc.’s sister brand for cosmetic chemists. She’s a member of the Council of Science Editors and Society of Cosmetic Chemists, and for the past several years, has led judging panels to honor the best ingredients in cosmetics.

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