Retinoids, what you need to know?

Tatyana Shalagina , cosmetologist-esthetician, author of the online project for advanced training of cosmetologists Skinstory Education

Retinoids are a vast topic, research on them is not yet complete and much remains to be understood. But today, in the hands of a competent specialist who understands the mechanics and nuances of use, retinoids can become an excellent tool and give the client the necessary long-term result, and the cosmetologist - job satisfaction.

According to the recommendations of many dermatological associations, retinoids are the first choice drugs for skin with acne [2]. They also do an excellent job of correcting pigmentation, photoaging and chronoaging [3, 4], improving skin texture, including reducing pore size [5]. By and large, retinoids are indicated for solving almost all major aesthetic skin imperfections, and the evidence base for them is large.

It should be noted that science has been studying retinoids for a long time, and the first article on topical retinoids on PubMed dates back to 1952. Retinoids are considered the first choice drugs for the correction of acne [6], which have been shown to increase the amount of collagen and extracellular matrix in the dermis [7] and help in the fight against photoaging [8] and hyperpigmentation.

The greatest number of scientific experiments concerns retinoic acid, or tretinoin, the final form of vitamin A conversion and not approved for use in cosmetics. Consequently, the cosmetic industry can only try to find alternative forms of retinoids that will be closest to retinoic acid, but are allowed in cosmetics.

And hydroxypinacolone retinoate , abbreviated HPR , recently became such a new retinoid ( Fig. 1 ). One of the options for its release is a raw material with the trade name Granactive Retinoid, or translated as “ granactive retinoid ” ( INCI: Dimethyl Isosorbide (and) Hydroxypinacolone Retinoate ). Granactive retinoid is a 10% solution of hydroxypinacolone retinoate in Dimethyl Isosorbide solvent. Therefore, if a product specifies 2% granactive retinoid, it means the product contains 0.2% hydroxypinacolone retinoate and 1.8% solvent. There are also other variations of HPR raw materials, such as a product branded SymRenew HPR, but these are less common.

Fig.1. Hydroxypinacone retinoate - HPR

Hydroxypinacolone retinoate is an ester of retinoic acid, therefore, it directly combines with its receptors and does not require preliminary enzymatic conversion in the cell. This theoretically makes it more active than retinol and retialdehyde. According to the manufacturer's studies, it has significantly less irritant potential compared to retinol when comparing 0.5% granactive retinoid (0.05% hydroxypinacolone retinoate) with 0.5% retinol [9]. But in fact, the ingredient is new, and there is not much research on it. My own experience confirms that the component works, but what does the science say?

One of the studies was sponsored by the giant Estee Lauder, therefore, it is better to take the results calmly, and it was also conducted on artificial skin. According to the study results, HPR had higher levels of transcription of retinoid-specific genes than after exposure to retinol, retinaldehyde and retinyl palmitate at the same concentrations, and was also less cytotoxic to cells at a 10-fold increase in concentration. However, HPR did not reach the level of gene transcription characteristic of retinoic acid [10]. From this it can be assumed that HPR is somewhere between retialdehyde and retinoic acid in activity.

HPR-treated skin significantly increased procollagen production compared to untreated skin and was comparable to that of retinoic acid. HPR did not induce a greater (or less) inflammatory response than retinoic acid or vehicle control [10]. The researchers conclude that HPR is an effective alternative to retinoic acid and other less potent retinoids in treating aging skin without harmful side effects.

There are also some predominantly Italian studies of combination drugs with HPR [11-13] along with salicylic acid, niacinamide or retinol in the fight against acne, but in such studies it is really difficult to understand the effect of HPR and separate it from the influence of other actives.

One of the advantages of HPR is the high stability of the molecule compared to other retinoids, the use of which in cosmetics is significantly limited by this fact, and also significantly affects the effectiveness of the drugs. Thus, hydroxypinacolone retinoate was very stable in the tested formulas at 25ºC for 6 months, 95% remained active. High chemical (but not physical, the product separated) stability was observed at a temperature of 40ºC for 3 months [14].

As for my own experience using HPR in practice, I am ready to believe in the effectiveness of this ingredient both against acne and against wrinkles and photodamage to the skin. I won't say that I see any less irritating potential, but as you know, the main cause of retinoic dermatitis is skin sensitivity. I believe that HPR should be introduced "in cretinoid steps" (gradual introduction for two weeks - every three days, two weeks - every other day and then every day) so that the skin has a chance to get used to it.

So, in my opinion, hydroxypinacolone retinoate is a really great new ingredient with a great future, and the evidence base for which should grow. Cosmetic chemistry does not stop in the search for “safer” alternatives to retinoic acid, and hydroxypinacolone retinoate is the result of such searches. Given my experience and proven ingredient stability, I am interested to see and work with more and more HPR products in the assortment of professional brands.

This article is part of a special project
"We work with the texture of the skin. The ideal combination for maximum results"

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Bibliography:

1. "Retinoids: groundless fears. Barriers to the prescription of cosmetics with retinoids", Shalagina T., Magazine "Pro Cosmetology by Cosmetologist" No. 4, 2021;
2. Zaenglein AL, Pathy AL, Schlosser BJ, Alikhan A, Baldwin HE, Berson DS, Bowe WP, Graber EM, Harper JC, Kang S, Keri JE, Leyden JJ, Reynolds RV, Silverberg NB, Stein Gold LF, Tollefson MM, Weiss JS, Dolan NC, Sagan AA, Stern M, Boyer KM, Bhushan R. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016 May;74[5]:945-73.e33. doi: 10.1016/j.jaad.2015.12.037. Epub 2016 Feb 17. Erratum in: J Am Acad Dermatol. 2020 Jun;82(6):1576. PMID: 26897386.
3. Randhawa M, Rossetti D, Leyden JJ, Fantasia J, Zeichner J, Cula GO, Southall M, Tucker-Samaras S. One-year topical stabilized retinol treatment improves photodamaged skin in a double-blind, vehicle-controlled trial. J Drugs Dermatol. 2015 Mar;14(3):271-80. PMID: 25738849.
4. Darlenski R, Surber C, Fluhr JW. Topical retinoids in the management of photodamaged skin: from theory to evidence-based practical approach. Br J Dermatol. 2010 Dec;163[6]:1157-65. doi: 10.1111/j.1365-2133.2010.09936.x. PMID: 20633013.
5. Endly DC, Miller RA. Oily Skin: A review of Treatment Options. J Clin Aesthet Dermatol. 2017 Aug;10[8]:49-55. Epub 2017 Aug 1. PMID: 28979664; PMCID: PMC5605215.
6. Zaenglein AL, Pathy AL, Schlosser BJ, Alikhan A, Baldwin HE, Berson DS, Bowe WP, Graber EM, Harper JC, Kang S, Keri JE, Leyden JJ, Reynolds RV, Silverberg NB, Stein Gold LF, Tollefson MM, Weiss JS, Dolan NC, Sagan AA, Stern M, Boyer KM, Bhushan R. Guidelines of care for the management of acne vulgaris. J Am Acad Dermatol. 2016 May;74(5):945-73.e33. doi: 10.1016/j.jaad.2015.12.037. Epub 2016 Feb 17. Erratum in: J Am Acad Dermatol. 2020 Jun;82(6):1576. PMID: 26897386.
7. Darlenski R, Surber C, Fluhr JW. Topical retinoids in the management of photodamaged skin: from theory to evidence-based practical approach. Br J Dermatol. 2010 Dec;163(6):1157-65. doi: 10.1111/j.1365-2133.2010.09936.x. PMID: 20633013.
8. Kafi R, Kwak HS, Schumacher WE, Cho S, Hanft VN, Hamilton TA, King AL, Neal JD, Varani J, Fisher GJ, Voorhees JJ, Kang S. Improvement of naturally aged skin with vitamin A (retinol). Arch Dermatol. 2007 May;143(5):606-12. doi: 10.1001/archderm.143.5.606. PMID: 17515510.
9. https://incidecoder.com/ingredients/hydroxypinacolone-retinoate
10. Anti-aging effects of retinoid hydroxypinacolone retinoate on skin models N Ruth1 and T Mammone2 1 Department of Skin Physiology & Pharmacology, Estee Lauder Companies, Melville, NY and 2 Department of Skin Physiology & Pharmacology/The Estee Lauder Companies, Melville, NY
11. Villani A, Annunziata MC, Cinelli E, Donnarumma M, Milani M, Fabbrocini G. Efficacy and safety of a new topical gel formulation containing retinol encapsulated in glycospheres and hydroxypinacolone retinoate, an antimicrobial peptide, salicylic acid, glycolic acid and niacinamide for the treatment of mild acne: preliminary results of a 2-month prospective study. G Ital Dermatol Venereol. 2020 Oct;155(5):676-679. doi: 10.23736/S0392-0488.20.06581-5. Epub 2020 Sep 1. PMID: 32869963.
12. Veraldi S, Barbareschi M, Guanziroli E, Bettoli V, Minghetti S, Capitanio B, Sinagra JL, Sedona P, Schianchi R. Treatment of mild to moderate acne with a fixed combination of hydroxypinacolone retinoate, retinol glycospheres and papain glycospheres. G Ital Dermatol Venereol. 2015 Apr;150(2):143-7. PMID: 25876142.
13. Veraldi S, Barbareschi M, Guanziroli E, Bettoli V, Minghetti S, Capitanio B, Sinagra JL, Sedona P, Schianchi R. Treatment of mild to moderate acne with a fixed combination of hydroxypinacolone retinoate, retinol glycospheres and papain glycospheres. G Ital Dermatol Venereol. 2015 Apr;150(2):143-7. PMID: 25876142.
14. Temova Rakuša Ž, Škufca P, Kristl A, Roškar R. Retinoid stability and degradation kinetics in commercial cosmetic products. J Cosmet Dermatol. 2021 Jul;20(7):2350-2358. doi: 10.1111/jocd.13852. Epub 2020 Dec 2. PMID: 33206444.

The article was published in the magazine "Pro Cosmetology by Cosmetologist" No. 1, 2022