The history of the discovery of retinoids dates back to Ancient Egypt, when the priests recommended eating raw animal liver to people suffering from night blindness. However, the external use of retinoids became possible only after the structure of the retinoic acid molecule was studied and chemists achieved success in its synthesis.
Already in 1943, the first work on the treatment of acne with vitamin A was published. In 1959, tretinoin was first used in dermatology, after which research on topical retinoids continued for several decades. In 1983, the first results of the use of tretinoin to reduce the manifestations of skin aging were published. Around the same time, pioneering researcher Albert Klingman introduced the new term – "cosmeceutical" which we still use today for the most active ingredients in external cosmetics.
In fact, the use of retinoids opened up new possibilities and became the basis for the creation of a new class of cosmetics. And although until today there is practically no legal restriction on the use of the term "cosmeceuticals" anywhere in the world (except Japan), any specialist understands what is meant when a product is called cosmeceutical.
Tiina Orasmäe-Meder
beautician
developer Meder Beauty Science
The main questions for classifying a drug as a cosmeceutical are:
1. Is it possible to achieve the penetration of the agent through the Stratum Corneum, maintaining the concentration necessary to obtain the effect, provided that the penetration rate is adequate, allowing to obtain a working concentration in a limited time?
2. Is there a known biochemical mechanism for the effect of the ingredient on the targeted layer of cells or certain tissues?
3. Are there studies conducted in accordance with the principles of evidence-based medicine (double-blind, placebo-controlled and statistically significant) confirming the effectiveness of the drug?
In cosmetology, there are very few ingredients and preparations for which you can get a positive answer to these questions. Retinoids were the first group of ingredients that we can talk about with confidence: yes, they penetrate into the deeper layers of the skin. Yes, the mechanism of their action is known. Yes, the effectiveness of retinoids has been confirmed by numerous studies.
Mechanism of action of retinoids
Retinoids are a group of natural and synthetic derivatives of vitamin A that are used in both pharmacological and cosmetic preparations. Retinoic acid (RA), as well as adapalene, tazarotene, bexarotene, – registered pharmacological agent. Retinyl esters, retinol, retinaldehyde and a group of oxyretinoids are used as local cosmeceuticals. All of them are used to reduce the manifestations of photoaging, acne, hyperkeratosis, wrinkles and some other dermatological problems.
Retinoic acid is more damaging than retinol and retinaldehyde. Some retinoic esters, in particular retinyl palmitate and retinyl acetate, have not been confirmed effective in correcting the manifestations of photoaging and are more often used not in cosmeceutical, but in cosmetic formulations. After penetration into the epidermis, retinol is transformed into retinaldehyde, which, in turn, is converted into retinoic acid, which has pharmacological activity.
Effectiveness of the product may vary depending on how complete the intradermal transformation of retinol occurs and the characteristics of the skin barrier: the faster and more complete absorption, the greater the effectiveness of the drug.
Retinoids are lipophilic and easily penetrate the epidermis. Interestingly, induction of the CP450-RAH enzyme occurs in the presence of retinoic acid in the skin, this enzyme serves as a marker of retinol absorption and transformation activity. This dependence is non-linear; with an increase in the concentration of retinol or retinaldehyde more than 0.025 percent – the possibility of its absorption by the skin ceases to increase, therefore the mentioned concentration is sufficient to achieve the effect.
According to studies, 75 percent of retinoids remain in the epidermis, about 20 percent penetrate the dermis, while only 40 percent of the retinoids in the epidermis are metabolized: the rest are not transformed and do not affect the skin structures.
What is the mechanism for achieving the effect of retinoids in various cosmetic problems?
Hyperpigmentation: Retinoic acid reduces the appearance of hyperpigmentation by enhancing and accelerating the renewal of epidermal cells. Due to the acceleration of maturation of keratinocytes, the contact time of melanocytes with keratinocytes decreases, which, in turn, reduces the melanosome-keratinocyte transfer, the intensity of staining of keratinocytes. As a result, there is a fairly rapid and noticeable lightening of hyperpigmented areas of the skin.
Fine and medium wrinkles: The reduction in the appearance of wrinkles primarily results from an increase in the epidermis' ability to retain moisture, due to the stimulation of the synthesis of glycosaminoglycans, transforming growth factor beta and procollagen, and therefore collagen.
Reduces dry skin by accelerating epidermal renewal. Retinoic acid binds to retinoid receptors of cells, resulting in increased expression of specific genes, primarily accelerating the maturation cycle of keratinocytes.
Special properties of retinoids
What is the difference between retinoids and other cosmetic ingredients? Not only the highest efficiency. The mechanism of action of retinoids is really peculiar. Their molecules penetrate the cell membrane by non-receptor endocytosis. In all eukaryotic cells, retinoids, and in particular tretinoin, quickly enter the cell nucleus with the help of CRABP (cellular protein that binds retinoic acid). This protein plays a key role in the bioavailability of retinoids.
The direct action of retinoids is carried out through retinoid receptors – RAR and RXR (retinoic acid receptors and retinoid X receptors). They are part of the "superfamily" of nuclear hormone receptors that are tropic for steroids, thyroid hormones, vitamin D, etc. The binding of a retinoid molecule to the receptor leads to the formation of receptor complex dimers, which, in turn, bind to specific DNA regions and activate certain regions. genes known as retinoid-specific elements (RRE). This completes the regulation of transcription of retinoid-responsive genes.
By and large, retinoids act as hormones by the mechanism of action. The dermal effects of this class of compounds are able to change depending on the activation or inhibition of enzymes responsible for the metabolism of retinoids in the skin, which may be the key to a more targeted effect, with a decrease in the number of side effects. An important feature of the dermal effect of retinoids – that they simultaneously inhibit the destruction of dermal collagen under the influence of external factors and enhance the synthesis of new collagen, primarily type I procollagen.
Skin softening with retinoids is due to the fact that retinoic acid, as confirmed by recent studies, is able to bind to serum albumin, cytokeratin 10 (having increased rigidity and synthesized in the epidermis under the influence of ultraviolet radiation or in the absence of vitamin A) and cytokeratin 16: this enhances regeneration and leads to softening and smoothing of the stratum corneum.
Given that the mechanism of operation of retinoids, even when applied topically, includes a confirmed effect on the cell nucleus and the genetic apparatus of cells, – the use of this class of ingredients during pregnancy and lactation is completely prohibited due to theoretically possible systemic effects, including effects on the fetus.
Local side effects of application are described as "retinoid reaction", or retinoid dermatitis. Unfortunately, the occurrence of this condition is almost inevitable, as well as a rapid increase in photosensitivity from the first days of therapy. Retinoids are phototoxic without being photoallergenic. In order to reduce the intensity of side effects, it is recommended to take into account the characteristics of these substances.
The effect of retinoids is always dose-dependent, therefore, to reduce the severity of dermatitis, it is recommended to limit yourself to single applications, preferably in the evening. It is possible to use retinoids several times a week, the application regimen every other day, etc. A good result is obtained by the simultaneous use of a three percent indomethacin or one percent hydrocortisone ointment.
The patient's attitude towards therapy matters. High expectations, lack of readiness for long-term use of retinoids and the inevitability of side effects at the beginning of therapy – often lead to refusal to use drugs and loss of therapeutic effect. Some dermatologists recommend applying moisturizing and nourishing products within 30 minutes of retinoid application. In addition, the use of sunscreen is mandatory during the entire treatment period. Cosmetic preparations, including beta-sisterone, extracts of ginkgo biloba, centella asiatica, are also recommended to alleviate the severity of dermatitis.
There is an alternative to retinoids in cosmetics
Given the rather high "payment for the effect" when using topical retinoids, it makes sense to pay attention to their derivatives, especially for the treatment of photoaging: retinaldehyde at a concentration of 0.05 percent, retinyl propionate and N-formyl aspartame have all the above-described stimulating qualities at better tolerability and fewer side effects.
Of course, the effect of using derivatives is somewhat slower, but the therapy is more comfortable and easier to tolerate. Some "retinoid" effects can be achieved with other ingredients. In particular, in the treatment of acne, one of the most important properties of retinoids – effect on the enzymatic activity of alpha-reductase, which is a key enzyme in chronic skin inflammation, as well as a rapid decrease in sebum secretion.
Avocutin has a similar efficacy and mechanism of action: when using a preparation containing 3% avocutin, sebum synthesis is reduced by approximately 30 percent during the first 14 days of daily use; at the same time, the activity of alpha-reductase is significantly reduced, which leads to a rapid decrease in skin oiliness and the number of inflammatory elements.
Manifestations of photoaging have been successfully corrected with agents that include tetrahexyldecyl ascorbate (one of the newer forms of ascorbic acid); this ingredient, as well as retinoids, affects the synthesis of structural proteins of the skin, reduces their UV-potentiated degradation, enhances the resistance and regenerative abilities of the skin and even the ability to retain moisture. However, tetrahexyldecyl ascorbate does not increase photosensitivity, does not have phototoxicity, its use is comfortable and is not associated with side effects.
It is important for the practitioner to remember that the use of retinoids, which have the highest efficacy, fully confirmed by clinical studies, at the same time implies a certain "price". The purpose of products containing this ingredient should be individual and deliberate. All side effects (retinoid dermatitis) should be discussed with patients in advance; it is advisable to immediately take measures to minimize discomfort: for example, in parallel with topical retinoids, prescribe a preparation based on Centella asiatica and a mild moisturizing and softening cream. In cases where the manifestations of photoaging are not too severe, acne occurs with mild or moderate severity, and the skin condition as a whole does not inspire alarm, – perhaps it makes sense to start by using alternative means,
According to ALLSEASON.RU
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