My Skincare Journey: Starting Over

Recently I decided to start my skincare routine from scratch so that I can better understand what products work better for me over others. To be frank, I never really took a scientific approach to it because my skin needs little maintenance overall (thanks genetics!). It definitely can use some improvements, though. Sometimes I have little spots of hyperpigmentation on my face and my nose can get pretty oily or flaky. The skin on my cheeks and forehead are the most low maintenance parts of my face, but I do think they could brighten up a bit!

I purchased Lab Muffin’s skincare book to see her suggestions on having a proper skincare routine. (Support scientific skincare and check out her book! I highly recommend it!) She suggests starting with only moisturizer and cleanser the first week, then adding an SPF, then slowly starting to add products to your routine one-by-one over the course of several weeks. 

I followed her plan and have ended up with a few empties. Overall I’ve noticed that my nose is less flaky since I’ve been better about moisturizing (I used to be so lazy). Here is a list of empties that I’ve just gone through, with some commentary on their formulas:

Missha Essence Sun Milk SPF 50+/PA+++

I bought this because I’m a sucker for the Korean skincare hype (not for any scientific reason--just after working in Seoul, I fell in love with their enthusiasm for skincare.) It’s most definitely not my favorite sunscreen because it feels a bit drying to me when applied on its own; I’m not surprised about this since the second ingredient on the list is denatured alcohol. What is nice about this product is that I think it pairs nicely with makeup. I never wear foundation, so this isn’t something I need. I prefer a more moisturizing sunscreen. It does feel nice in the summer since it isn’t super heavy.

Its top ingredient is from a plant called dwarf everlasts. I have no idea what those plants even are and what the extract is from (i.e. its stem, leaves, flowers). This is something I need to look more into. My knowledge on the efficacy and composition of plant extracts is wanting, but that’s the beauty of cosmetic science, right? Never-ending learning.

Would I purchase this again? Probably not. I’ll write about it in a separate post, but I’m now trying Black Girl Sunscreen SPF 30, and I like the formula so far!

INGREDIENTS: Helichrysum Arenarium Extract, Alcohol Denat., Ethylhexyl Methoxycinnamate, Octocrylene, Ethylhexyl Salicylate, Butylene Glycol, Butyl Methoxydibenzoylmethane, Methyl Methacrylate Crosspolymer, Silica, Althaea Rosea Root Extract, Bis-Ethylhexyloxyphenol Methoxyphenyl Triazine, Rosa Davurica Bud Extract, Portulaca Oleracea Extract, Nelumbo Nucifera Flower Extract, Aloe Barbadensis Leaf Extract, Abronia Villosa Leaf Extract, Cinchona Succirubra Bark Extract, Rhodiola Rosea Root Extract, Psidium Guajava Leaf Extract, Limonia Acidissima Extract, Camellia Sinensis Leaf Extract, Pueraria Lobata Root Extract, Diospyros Kaki Leaf Extract, Morus Alba Fruit Extract, Artemisia Princeps Leaf Extract, Cinnamomum Cassia Bark Extract, Chrysanthemum Indicum Flower Extract, Camellia Japonica Flower Extract, Prunus Mume Flower Extract, Calendula Officinalis Flower Water, Pelargonium Graveolens Flower Water, Salvia Officinalis (Sage) Water, Dimethicone, Nylon-12, Acrylates/​C10-30 Alkyl Acrylate Crosspolymer, BHT*, Sodium Hydroxide, Betaine, Caprylyl Methicone, Methoxy PEG/​PPG-25/​4 Dimethicone*, Bis- PEG/​PPG-20/​5 PEG/​PPG- 20/​5 Dimethicone*, Caprylic/​Capric Triglyceride, Disodium EDTA*, Caprylyl Glycol, Ethylhexylglycerin, 1,2-Hexanediol, Fragrance

*The original ingredient list read these ingredients as: “Bht,” “Peg,” “Ppg,” and, “Edta.” It’s a little of a pet-peeve of mine to see ingredient lists not properly capitalized.

INGREDIENT BREAKDOWN:

• Plant Extracts: Helichrysum Arenarium Extract, Althaea Rosea Root Extract, Rosa Davurica Bud Extract, Portulaca Oleracea Extract, Nelumbo Nucifera Flower Extract, Aloe Barbadensis Leaf Extract, Abronia Villosa Leaf Extract, Cinchona Succirubra Bark Extract, Rhodiola Rosea Root Extract, Psidium Guajava Leaf Extract, Limonia Acidissima Extract, Camellia Sinensis Leaf Extract, Pueraria Lobata Root Extract, Diospyros Kaki Leaf Extract, Morus Alba Fruit Extract, Artemisia Princeps Leaf Extract, Cinnamomum Cassia Bark Extract, Chrysanthemum Indicum Flower Extract, Camellia Japonica Flower Extract, Prunus Mume Flower Extract, Calendula Officinalis Flower Water, Pelargonium Graveolens Flower Water, Salvia Officinalis (Sage) Water

• Solvents: Alcohol Denat.; Butylene Glycol; 1,2-Hexanediol*

  • *Typical solvent for preservatives

• Sunscreens: Ethylhexyl Methoxycinnamate, Octocrylene, Ethylhexyl Salicylate, Butyl Methoxydibenzoylmethane, Bis-Ethylhexyloxyphenol Methoxyphenyl Triazine

• Polymer: Methyl Methacrylate Crosspolymer

• Texturizers: Silica, Nylon-12

• Emollients: Dimethicone, Caprylyl Methicone, Caprylic/​Capric Triglyceride

• Emulsifiers: Acrylates/​C10-30 Alkyl Acrylate Crosspolymer, Betaine, Methoxy PEG/​PPG-25/​4 Dimethicone, Bis- PEG/​PPG-20/​5 PEG/​PPG- 20/​5 Dimethicone

• Antioxidant: BHT

• pH Adjuster: Sodium Hydroxide

• Chelating Agent: Disodium EDTA

• Preservative: Caprylyl Glycol, Ethylhexylglycerin,

• Fragrance

Versed Dew Point Moisturizing Gel-Cream

A very straightforward, Sepigel 305-based gel-cream. I think if you’re a budding cosmetic chemist/beginning formulator, this is an easy formula to learn how to deformulate.

I purchased this because I want to explore cheaper brands and my husband is a huge fan of gel-creams. Me? Not so much. And this gel-cream didn’t wow me much either. I definitely won’t purchase this again, but I’m glad I got it so I can use it as a teaching tool for my ecourse. 

My issue with this formula is that it’s not moisturizing enough. (Are you starting to see a pattern in the types of formulas I like?) My husband and I like different textures when it comes to moisturizers--I love the after-feel of lots of glycols and emollients; I want to feel like something is left on my face. My husband prefers formulas with an almost matte dry-down.

Again, this would be a nice formula to pair with makeup since the dry-down after application is pretty quick in my opinion. It does get the job done when the weather isn’t blistering cold, but I definitely didn’t like this formula on colder days. It felt like my skin was drying up and I needed to reapply it.

INGREDIENTS: Water, Glycerin, Propylene Glycol, Squalane, Aloe Barbadensis Leaf Juice, Camellia Sinensis Leaf Extract, Simmondsia Chinensis (Jojoba) Seed Oil, 1,2-Hexanediol, Phenoxyethanol, Carbomer, Polyacrylamide, Triticum Vulgare (Wheat) Germ Oil, C13-14 Isoparaffin, Sodium Hydroxide, Sambucus Nigra Flower Extract, Laureth-7, Trisodium Ethylenediamine Disuccinate, Sodium Hyaluronate, Potassium Sorbate, Sodium Benzoate, Citric Acid

INGREDIENT BREAKDOWN:

• Solvents: Water; 1,2-Hexanediol*

  • *Typical solvent for preservatives

• Humectants: Glycerin, Propylene Glycol, Sodium Hyaluronate

• Emollients: Squalane, Simmondsia Chinensis (Jojoba) Seed Oil, Triticum Vulgare (Wheat) Germ Oil

• Plant Extracts: Aloe Barbadensis Leaf Juice, Camellia Sinensis Leaf Extract, Sambucus Nigra Flower Extract

• Preservatives: Phenoxyethanol, Potassium Sorbate, Sodium Benzoate

• Thickening Agent: Carbomer

• Emulsifier: Sepigel 305 (Polyacrylamide, C13-14 Isoparaffin, Laureth-7)

• pH Adjusting Agents: Sodium Hydroxide, Citric Acid

• Chelating Agent: Trisodium Ethylenediamine Disuccinate

Simple Micellar Water

This is my when-I’m-lazy-and-don’t-want-to-wash-my-face “cleanser.” Micellar waters contain mild surfactants solubilized in water with other doo-dads. This formula contains a surfactant called PEG-6 caprylic/capric glycerides. Glycerides are gentler on the skin compared to sulfates (I don’t think you’d generally find sulfates in micellar water). The formula also contains cetrimonium chloride which is a cationic surfactant that attracts to the negative charges on skin (due to the positively charged cetrimonium) and “conditions” it. In other words, it helps to make this formula feel less harsh on skin when you use it to “cleanse” it.

I am a true sinner with this product--I use it to wipe off my liquid eyeliner (either Benefit’s Roller Liner or Em Cosmetics liner), my cheeks, my forehead, and then I’m done. Do I rinse? No. See? Fucking sinner. Perhaps I shouldn’t even purchase micellar water in the future because of how lazy it makes me.

(Note: Since I originally drafted this blog post a few weeks ago, I’m happy to say I’ve barely used it since then and have been much better at washing my face at the end of the day even though I’m so tired.)

INGREDIENTS: Aqua, Hexylene Glycol, Glycerin, Niacinamide, Panthenol, Chamomilla Recutita Flower Extract, PEG-6 Caprylic/​Capric Glycerides, Butylene Glycol, Pantolactone, Cetrimonium Chloride, Tetrasodium EDTA, Citric Acid, Potassium Chloride, Sodium Ascorbyl Phosphate, Sodium Chloride, Dmdm Hydantoin, Iodopropynyl Butylcarbamate.

INGREDIENT BREAKDOWN:

• Solvents: Aqua (Water), Hexylene Glycol, Glycerin

• Vitamins: Niacinamide (B3), Panthenol (B5), Sodium Ascorbyl Phosphate (C)

• Plant Extracts: Chamomilla Recutita Flower Extract

• Surfactants: PEG-6 Caprylic/Capric Glycerides, Cetrimonium Chloride

• Humectants: Butylene Glycol, Pantolactone

• Chelating Agent: Tetrasodium EDTA

• pH Adjuster: Citric Acid

• Viscosity Adjusting Agents: Potassium Chloride, Sodium Chloride

• Preservatives: DMDM Hydantoin, Iodopropynyl Butylcarbamate

Drunk Elephant Beste No. 9 Jelly Cleanser

I got this cleanser as a free sample, and I like it a lot. When I first started using it, it felt like it made my skin pretty dry. But as I got used to it, I didn’t feel like it’s as bad as, say, a sulfate-based cleanser. I felt like my skin was quite clean.

Drunk Elephant’s formulations, from what I’ve used, are pretty standard “natural” but nice formulas. They’re not innovative since they use the common “natural” ingredients offered by suppliers. As a brand, I’m starting to learn some questionable things about their ethics (and I just purchased their Protini Cream to deformulate, oops.) Perhaps in the future I won’t support this brand anymore, but for now, I think that learning how to de-formulate their products is good for formulation practice (minus all of the peptides they add which I have to research more about in terms of their efficacy). 

From a formulation standpoint, I say most of the common “natural” ingredients here are propanediol (aka Zemea propanediol) and coco-glucoside. Propanediol is derived from corn and coco-glucoside is derived from coconut (the “coco” part of the name gives you the hint of its origin.) 

INGREDIENTS: Water, Glycerin, Cocamidopropyl Betaine, Coco-Glucoside, Sodium Lauroyl Methyl Isethionate, Cocamidopropyl Hydroxysultaine, Sodium Methyl Oleoyl Taurate, Propanediol, Aloe Barbadensis Leaf Extract, Glycolipids, Linoleic Acid, Linolenic Acid, Lauryl Glucoside, Cucumis Melo Cantalupensis Fruit Extract, Sclerocarya Birrea Seed Oil, Dipotassium Glycyrrhizate, Tocopherol, Citric Acid, Phenoxyethanol, Sodium Hydroxide, Sodium Benzoate, Sodium Chloride, Polylysine

INGREDIENT BREAKDOWN:

• Solvent: Water

• Humectants: Glycerin, Propanediol

• Surfactants: Cocamidopropyl Betaine, Coco-Glucoside, Sodium Lauroyl Methyl Isethionate, Cocamidopropyl Hydroxysultaine, Sodium Methyl Oleoyl Taurate, Lauryl Glucoside

• Plant Extracts/Oil: Aloe Barbadensis Leaf Extract, Cucumis Melo Cantalupensis Fruit Extract, Sclerocarya Birrea Seed Oil

• Skin Conditioning Agent: Glycolipids

• Amino Acids: Linoleic Acid, Linolenic Acid, Polylysine

• Soothing Agent: Dipotassium Glycyrrhizate

• Antioxidant: Tocopherol

• pH Adjusters: Citric Acid, Sodium Hydroxide

• Preservatives: Phenoxyethanol, Sodium Benzoate

• Viscosity Adjusting Agent: Sodium Chloride

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I’ll write more about this later on, but I also recently incorporated The Ordinary’s Glycolic Acid Solution into my routine mostly for my oily nose. It’s worked great so far, but I’ve always been a fan of glycolic acid since I was a wee chemist. 

What are you using now?

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Hey, boosuke! Did you find something not factual in this blog post? Leave a comment and let me know! Although I teach a beginning cosmetic formulation course, I will never feel like a master in the craft of formulation. Why? Because I never want to stop learning. I prefer to be (kindly!) corrected so that I can keep improving my craft.

Be respectful in the comments. Cosmetic science has become a contentious topic over the years due to rampant misinformation perpetuated by the internet and ignorant/dishonest brands. Let’s facilitate friendly discussion and assume (at first) that everyone is coming from a good place.

Hyaluronic Acid

Hyaluronic acid has become quite the buzz ingredient over the past couple of years. I personally love it, but a fellow cosmetic chemist has challenged me in believing in its efficacy. This chemist believes that at the current levels it’s normally used in cosmetics, ~0.1 - 10% w/w*, it has little to no benefit for the skin. So! The purpose of this blog post is to look at current literature and a) understand what the molecule is, b) understand how it works on skin, and c) see what amount is considered efficacious.

What is hyaluronic acid?

Hyaluronic acid is a high molecular weight carbohydrate. How heavy? Think several thousands of sugars in one chain! It occurs naturally in all living organisms and is produced in our Golgi apparatus. One link in this chain is a dimer of D-glucuronic acid and N-acetylglucosamine.

It serves many purposes in our body, one of them being keeping our joints lubricated. The main feature of this molecule is that it’s extremely hygroscopic, aka it looooooves water. In fact, it’s one of the most hydrophilic molecules in nature. Why is that?

That’s because of the oxygens on the chains. If you recall from high school chemistry, oxygens can bond to hydrogen via hydrogen bonds. Thus, these oxygens on hyaluronic acid are attracted to the hydrogens in a water molecule. What happens when this molecule binds with water? It stiffens and expands into a random coil that traps about 1,000 times its weight in water.

Need a review of high school chemistry spoken in terms of cosmetic chemisTRY? I got you covered.

Hyaluronic acid occurs as the salt form, hyaluronate, in our skin. Why? Skin pH is at about 4.3 - 4.5, but hyaluronic acid’s pKa is 3 - 4. Remember that if the environment the molecule is in is higher than its pKa, it becomes ionized and the oxygens in hyaluronic acid lose their hydrogens to become O-. However, hyaluronate isn’t just found there! It’s also found in the umbilical cord, synovial fluid, vitreous humor, lung, kidney, brain and muscle tissues!

How does hyaluronic acid work?

Hyaluronic acid is a humectant. For skincare, its main function is to help the skin maintain moisture when it’s applied topically. This is possible due to its aforementioned hygroscopic nature. Since it attracts water toward it, it reduces the likelihood that the skin will lose water. It may also bring extra water to the skin, but how much varies a lot with the formula it’s in and the environment you’re in when you apply it. For example, a more humid environment will have more water in the atmosphere for hyaluronic acid to attract toward your skin. This attraction to water helps to prevent transepidermal water loss (TEWL), meaning that it helps to reduce the amount of water that evaporates from your skin. 

Another thing to consider is the effect of hyaluronidase on the skin. Hyaluronidase is a class of enzymes which break down hyaluronic acid into smaller parts. Now remember, hyaluronic acid is a chain of carbohydrates. Hyaluronidases break up these large chains into smaller parts. The question then becomes, is this a good thing or a bad thing? Milani et al (2017)  found that the effects of hyaluronic acid could be limited due to the existence of hyaluronidase since it isn’t easily measured and understood how long hyaluronic acid stays on your skin before it’s degraded, and this assumes that the formula delivers all of the hyaluronic acid to your skin without you rubbing it off.

I couldn’t find literature commenting on how much and which type of hyaluronidase is on your skin to render this point appreciative, but it is something to consider when thinking about the efficacy of hyaluronic acid. Also, not all skin is created equal. Do certain people have a greater concentration of hyaluronidases on their skin compared to others? Who has more and who doesn’t? Does hyaluronic acid work better on people who have less hyaluronidases in their stratum corneum? Or does it not make an appreciative difference? One of the hyaluronidases in humans is  Hyal-2 which works in pH 6 - 7. Since the skin is more acidic (pH 4.3 - 4.5), how does this affect the functionality of Hyal-2? What is the optimal pH for the other four hyaluronidases that exist in humans?

On the flip side, smaller molecular weight hyaluronic acid could better penetrate the skin to draw in water into deeper layers of the stratum corneum. Laugier et al (2001)  tested an unknown molecular weight of hyaluronic acid in both cadaver and synthetic human skin and found that hyaluronic acid did not appreciably penetrate the stratum corneum. I would love to know which hyaluronic acid salt they used from Sigma so we could see if their conclusion corroborates with other research. Meanwhile, Brown et al (1999) found that 400 kDa hyaluronic acid could penetrate to the dermis.

Does hyaluronic acid need to penetrate (incorporate into) the skin?

A paper from Bos et al (2000) talks about how chemical compounds can’t penetrate the skin unless they are 500 Da, which is way smaller than the molecular weights of hyaluronic acid chains typically out on the market (e.g. Making Cosmetics sells an 8000 Da one). Although this paper acknowledges that molecules larger than 500 Da have been demonstrated to penetrate the skin, can we be sure the hyaluronic acid out on the market is actually penetrating? Does it need to? 

It can probably make a difference if it penetrates the skin since it’ll be able to bring moisture in at a deeper level, but it can still be helpful sitting on top of your stratum corneum. Some research has suggested that lower molecular weight hyaluronic acid can penetrate the stratum corneum, but what is not clear to me is how helpful that is. Even if you had a small enough molecule, it’d only be able to penetrate the skin through a polar pathway. Is that amount appreciable enough to show improved moisturization?

Need a refresher on skin penetration? Check out my blog post here!

Can hyaluronic acid improve wrinkles?

There’s evidence that wrinkle reduction can be improved via injection of hyaluronic acid, but based on present literature, topical hyaluronic acid is an anti-aging ingredient in the sense that it maintains your skin’s health by keeping it moisturized. Pavicic et al (2011) suggests that it may have anti-inflammatory effects which relate to anti-aging, but they haven’t published any studies that I can find which demonstrate this. In general, research suggests that moisturization helps to maintain homeostasis of your skin, and thus the health and integrity of it too (aka less wrinkles).

So is hyaluronic acid or sodium hyaluronate better for your skin?

Depending on the pH of the actual product, you will generally have one or the other form in your product. Why? Let’s not forget the pKa! If a formulator were to add hyaluronic acid in a formula but its final pH is above 4, most likely the hyaluronic acid has deprotonated to turn into the salt form, hyaluronate.

Thinking about the acid versus the salt form, both forms should be able to hydrogen bond with water. The salt form should also be able to have an ion-dipole interaction with water due to the negative charge on oxygen. Since ion-dipole interactions are stronger than hydrogen bonds, does this mean that sodium hyaluronate is better for your skin since the chemistry says it should have a stronger attraction to water? I don’t know! Is there even a difference? I couldn’t find any literature out there which points out which form of hyaluronic acid is better, but please share with me if you have found otherwise!

Do you need a mix of molecular weights to achieve optimal moisturization?

Pavicic et al (2011) tested different 0.1% w/w hyaluronic acid creams, each containing either 50, 130, 300, 800, and 2000 kDa chains. The test subjects were 30 - 60 year old Caucasian women, the experimental design seemed sound, and their base formula was a pretty basic cream. Overall based on their published data from this in vivo study, it does look like the 50 kDa cream showed the best results over a period of 30 and 60 day period.

Jegasothy et al (2014) demonstrated that nano-sized hyaluronic acid has even more efficacy, but this study holds no weight for me. They did not describe the type of formula they used and they had no control, so what am I really looking at when there’s nothing to compare or asses?

I haven’t found any data that proves that a mix of molecular weights is optimal like The Ordinary claims, but I can see the logic in it. If you have some lower molecular weight hyaluronic acid that penetrates deeper into the stratum corneum and then some higher molecular weight ones that sit on top, then you have a variety of hyaluronic acid molecules distributed across different layers of your stratum corneum to bring more moisture throughout the skin. Is this better than concentrating hyaluronic acid in one layer? Not sure. I’d like to see a study on that, though.

Is hyaluronic acid natural? Where does our hyaluronic acid come from? Humans!?

No, it doesn’t. You can produce hyaluronic acid by the fermentation of glucose and yeast extract. Making Cosmetics supplies a hyaluronic acid made from glucose, soy peptone and yeast extract.

Is hyaluronic acid safe?

The last published report by the CIR in 2009 concluded that hyaluronic acid and its salts are safe when looking at cosmetics with up to 2% w/w. They acknowledge that there are data gaps and other concentrations they need to consider. It was discussed during the December 9-10, 2019 expert panel meeting, so I look forward to seeing more conclusions from them. I think it was important for the panel to reconvene considering that many cosmetic products in the market are definitely over 2% w/w.

Formulation Tips

Lower molecular weight hyaluronic acid is easier to mix than higher molecular weight ones since the higher molecular weight one has a thickening effect. When a formula, namely the water phase, is thickened by hyaluronic acid, it tends to have a psuedo-plastic rheology. If you’re working with hyaluronic acid powder, you need to carefully sprinkle it into the vortex of your water with mixing to prevent clumping of the powder. If you’re an at home formulator, Making Cosmetics sells a 8 - 15 kDa hyaluronic acid that should be easier to mix. I think though if you just want to make your life easier, get a sodium hyaluronate solution and put that in your water phase.

Final Opinion--is Hyaluronic Acid Bullshit or Not?

After my personal research, I do feel that including hyaluronic acid in your skin care routine can have a positive impact more or less. I don’t feel, however, it’s the super ingredient brands will have you believe it is. I personally love The Ordinary’s Hyaluronic Acid Serum, but also keep in mind that from anecdotal experience, I’ve been genetically blessed with low maintenance skin (a lot of times I don’t wear a lot of products). I do feel that using the serum before moisturizing gives my skin more relief when it’s really dry.

I can see where my friend’s doubt lies as I haven’t come across a lot of literature with good experimental design to demonstrate hyaluronic acid’s efficacy aside from some pieces of literature above. I think hyaluronic acid can help reduce TEWL and help with dry skin. Is it an anti-aging ingredient? Well, it moisturizes you. That’s about my main takeaway from what we know about the ingredient.

If you have any interesting data to share with me, I’d love to see it!

*w/w = weight per weight. Formulas are written by cosmetic chemists by how much they weigh, not by volume.

References

1. Miller, William H. Muller and Kirk's Small Animal Dermatology. 7th ed., Elsevier Health Sciences, 2013.

2. Milani, M. and Sparavigna, A. “The 24-hour skin hydration and barrier function effects of a hyaluronic 1%, glycerin 5%, and Centella asiatica stem cells extract moisturizing fluid: an intra-subject, randomized, assessor-blinded study.” Clinical, Cosmetic and Investigational Dermatology. 2017 Aug 11;10:311-315. doi:10.2147/CCID.S144180

3. Harada, H. and Takahashi, M. “CD44-dependent intracellular and extracellular catabolism of hyaluronic acid by hyaluronidase-1 and -2.” J Biol Chem. 2007 Feb 23;282(8):5597-607. doi: 10.1074/jbc.M608358200

4. Pavicic, T. et al. “Efficacy of cream-based novel formulations of hyaluronic acid of different molecular weights in anti-wrinkle treatment.” J Drugs Dermatol. 2011 Sep;10(9):990-1000. PMID: 22052267

5. Jegasothy, S Manjula et al. “Efficacy of a New Topical Nano-hyaluronic Acid in Humans.” The Journal of clinical and aesthetic dermatology vol. 7,3 (2014): 27-9.

6. Bukhari, SNA et al. Int J Biol Macromol. 2018 Dec;120(Pt B):1682-1695. doi: 10.1016/j.ijbiomac.2018.09.188.

7. Bos, J.D. and Meinardi, M.M.H.M. “The 500 Dalton rule for the skin penetration of chemical compounds and drugs.” Exp Dermatol. 2000;9:165-169. doi: 10.1034/j.1600-0625.2000.009003165.x

8. Laugier, J.P. et al. “Topical hyaluronidase decreases hyaluronic acid and CD44 in human skin and in reconstituted human epidermis: evidence that hyaluronidase can permeate the stratum corneum.” Br J Dermatol. 2001 Dec 24;142(2):226-233. doi:10.1046/j.1365-2133.2000.03289.x

9. Brown, T.J. et al. “Absorption of hyaluronan applied to the surface of intact skin.” J Invest Dermatol. 1999;113:740-746.

10. Becker, L.C. et al. “Final report of the safety assessment of hyaluronic acid, potassium hyaluronate, and sodium hyaluronate.” Int J Toxicol. 2009 Jul-Aug;28(4 Suppl):5-67. doi: 10.1177/1091581809337738.