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Tretinoin is a retinoid, which are natural or synthesized forms of Vitamin A[1].Tretinoin is also known as all-trans retinoic acid and it available with a prescription. Other retinoids such as retinol and its esters are available over the counter[1]. They are used in topical treatments for various dermatological conditions[1]. Tretinoin can be used for the treatment of photodamage, melasma, and acne[1]. It works by increasing skin cell turnover rate, allowing a new layer to be seen on the skin sooner[2].

How it works

Retinoids are applied directly onto the skin, where they can diffuse into the dermal cells as they can diffuse through cellular membranes[2]. Once inside of the cell, they bind to nuclear receptors and change the gene expression of certain epidermal genes[2]. They then increase the rate of cell turnover by increasing the rate cells proliferate and differentiate[2]. This means that more cells are being made and becoming skin cells. Retinoids counter the effects of aging that lead to a thinning of the epidermis and dermis[2]. Because of aging and environmental factors, keratinocyte turnover can decrease[2]. This causes the epidermis to thin[2]. The thinning of the dermis can be due to various reasons, which include the decreased amount of fibroblasts and the synthesis of collagen[2]. Matrix metalloproteinases can also increase collagen degradation, causing dermal thinning[2]. However, retinoids work to counter these effects[2]. They increase the synthesis of collagen and fibrillin while decreasing the production of matrix metalloproteinase. The combination of all the processes tretinoin affects allows skin to remain younger looking by increasing the rate of cell turn over. New cells are consistently being brought to the surface more often.


Because of side effects, tretinoin needs to be introduced to the skin gradually. The skin needs to build up a tolerance to irritating chemical. Although application instructions or recommendations may differ for individuals, a general application schedule is as follows: It is usually recommended to apply tretinoin to the skin twice a week at night at first[2]. The following week, it is recommended to apply it three times a week at night[2]. Then, users may apply it every other day[2]. Once tolerance is built up, users may apply tretinoin every night after cleansing[2]. However, if any side effects are experience, it is recommended to apply less often until irritation decreases[2]. Tretinoin works in three month cycles[2]. Users of tretinoin may experience those side effects at first, but after three months they could mostly disappear and leave the user with their desired result[2].

Side effects

Tretinoin can be very irritating to the skin as it is not stable[1][2][3]. It can cause dryness, skin flaking, and redness[2]. The skin appears irritated if it cannot tolerate tretinoin, which is why building a tolerance is important[2]. It is also important to moisturize skin while using tretinoin to avoid redness and peeling. To prevent side effects and protect the more vulnerable skin, sunscreen should be used as well[2]. Tretinoin causes a high cell turn over rate, meaning there is always new, fresh skin on the surface instead of a layer of dead skin cells. Because of this, the skin being treated with tretinoin is vulnerable. Sunscreen is essential protect the new skin cells from being damaged by sun. Using other harsh chemicals such as salicylic acid while also tretinoin is not recommended as it could increase the chance of having side effects or the severity of them.

Delivery of Tretinoin

The delivery method of tretinoin can impact its efficacy and potential side effects. Because of this, the method by which tretinoin is topically delivered is important. One method is using chitosan-lipid nanoparticles as carriers[1]. Chitosan-lipid nanoparticles exhibit antibacterial activity[1]. This is useful for both storing tretinoin without bacterial containments it and to be used in combination against acne caused by bacteria[1]. Chitosan-lipid nanoparticles are very stable[1]. They have allowed tretinoin to be safely stored for at least a year[1]. As they have great physical stability, tretinoin works effectively on the skin[1]. Chitosan-lipid nanoparticles production does not require the use of organic solvents. Because of this, they are fairly easy to produce and provide a good way to effectively supply tretinoin.

Treatment of different skin conditions

Tretinoin is used to treat many skin conditions such as photodamage, melasma, and acne. Photodamage refers to dry skin, deep wrinkles, saggy skin, and discoloration due to long term exposure to the sun[2]. Melasma is a discoloration of the skin that can potentially be due to long term sun exposure as well, but can have other causes such as hormone activity, stress, genetics, and reactions to certain medications[4]. Application of tretinoin may relieve these symptoms[2][4]. Tretinoin decreases the severity of dermal wrinkles, increases skin firmness, and improves skin tone[2]. It also works to even out skin pigmentation and improve discolorations[2][4]. Acne is also improved by the use of tretinoin. Because tretinoin brings new cells to the surface, skin pores do not have that much of a chance to get clogged with old, dead skin cells as they are consistently being sloughed off the surface of the skin. Also, tretinoin will aide in the disappearance of old acne scars by renewing the skin affected by the scar.

Comparison of Tretinoin to OTC retinoids

Retinoids are derivatives of vitamin A[1][2][3]. There are various forms, which are often used as an anti-aging treatment[2]. Tretinoin is a form that is only available by prescription, while retinol is form available over the counter[2]. Various studies compare the effect of prescription and over-the-counter retinoids[2]. When compared, improvement is seen in both and the difference between the groups was not significant[2]. All saw the improvements in their skins’ texture and appearance[2]. Many creams at the drugstore carry products that include retinols, so a prescription from a dermatologist is not necessary to use a retinoid.


  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 Ridolfi, DM, PD Marcato, GZ Justo, et al. 2011. Chitosan-solid lipid nanoparticles as carriers for topical delivery of tretinoin. Colloids Surf B Biointerfaces. Epub ahead of print.
  2. 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 2.19 2.20 2.21 2.22 2.23 2.24 2.25 2.26 2.27 2.28 2.29 2.30 Ho, ET, NS Trookman, BR Sperber, et al. 2012. A Randomized, Double-Blind, Controlled Comparative Trial of the Anti-Aging Properties of Non-Prescription Tri-Retinol 1.1% vs. Prescription Tretinoin 0.025%. J Drugs Dermatol. 11(1):64-9.
  3. 3.0 3.1 Faghihi, G, A Shahingohar, and AH Siadat. 2011. Comparison between 1% tretinoin peeling versus 70% glycolic acid peeling in the treatment of female patients with melasma. J Drugs Dermatol.10(12):1439-42.
  4. 4.0 4.1 4.2 Situm M, M Kolić, Z Bolanca, et al. 2011. Melasma--updated treatments. Coll Antropol. 35 Suppl 2:315-8.