Acid Peels: Chemistry, Formulations, and Mechanisms

Chemistry of Peels and Biochemical Interactions

• Understanding the chemistry of peels and their interaction with the skin's biochemical components is crucial.
• Key considerations for selecting a chemical peel:
  • Molecular weight (Dalton weight) of the peeling ingredient.
  • Biochemical reactions within the skin.
  • Polarity of the molecule (polar vs. non-polar).
  • Concentration of the active ingredient.
  • pH and pKa of the solution.
  • Whether the solution has been partially neutralized.

Molecular Weight (Daltons)

• Molecules below 500 Daltons can generally penetrate the skin passively.
• This penetration occurs without significant interruption or the need for penetration-enhancing procedures/ingredients.
• In a previous class, Dalton weights of glycolic acid, lactic acid, and salicylic acid were calculated.

Biochemical Reactions in the Skin

• Understanding these reactions is essential, and they will be discussed in relation to specific peel types.

Polarity of Molecules

• Peel ingredients can be polar or non-polar.
• Extremes in polarity (very polar or very non-polar) tend to be less effective at penetrating the skin.
• Smaller molecules with a balance of polar and non-polar qualities often penetrate best.
• Non-polar molecules may penetrate the lipid bilayers of the stratum corneum more easily, which is often the target area for peels.

Concentration and pH

• The concentration of the active ingredient affects the resulting pH of the solution.
• pH and pKa are important factors to consider, as well as whether the solution needs to be neutralized or is already partially neutralized.

Form of the Vehicle

• The formulation of the product (vehicle) influences the peel's effects and how it needs to be handled.
• Different forms:
  • Liquid (watery consistency)
  • Gel (thickened watery consistency)
  • Cream
  • Powder

Liquid Peels

• Often have a watery consistency.
• Applied using a dappen dish with a fan brush or gauze.
• Require only a small amount for application.
• Demand more caution and control due to their runny nature.
• Avoid overly wet brushes or gauze to prevent dripping and uneven coverage.
• The patient should be positioned at a slight incline (45-degree angle) in a treatment couch to avoid the peel running into the eyes and mouth.
• Pooling can occur in skin folds, leading to concentrated effects in those areas (e.g., around the nose and mouth).
• Aqueous solutions are common, especially for alpha hydroxy acids (AHAs).
• Some peeling agents, like salicylic acid, are dissolved in alcohol (e.g., ethanol).
• Alcohol-based solutions can have a cooling effect due to evaporation.
• Evaporation of alcohol can lead to recrystallization of the acid on the skin's surface, causing pseudo-frosting.

Pseudo Frosting

• The re-precipitation of salicylic acid out of solution as the alcohol evaporates.
• Presents as a white cast on the skin.
• Can help indicate even application.
• Must be distinguished from true blanching or frosting, which indicates tissue damage (kernelysis).
• Pseudo-frosting looks more even overall, while true frosting appears in hot spots where there is damage to the tissues.
• The client's sensation of the peel is crucial; dialogue should be maintained throughout the procedure, so we remain in contact with the client.

Gel Formulations

• Becoming more common due to better control during application.
• Require a thickener (gum thickeners or synthetic polymer thickeners).
• Historically, many thickeners were pH-sensitive, but more pH-insensitive options are now available.
• Reduce the risk of drips and pooling, leading to more even coverage.
• The thicker consistency can slow the diffusion of the acid into the skin (Fick's equation: dissociation constant).
• Slower delivery increases safety and is often better tolerated by sensitive skin types and those with vascular conditions or impaired barrier function.
• Often water-based with humectants, helping to hydrate the skin and prevent the peel from drying out.

Salicylic Acid Gels

• Increasingly, salicylic acid is formulated in a polyethylene glycol (PEG) base instead of ethanol.
• This eliminates the pseudo-frosting effect because there is no rapid evaporation.
• The PEG base helps to keep the skin hydrated, promoting better penetration and peeling action.
• Water is required to break apart proteins in the peeling process (hydrolysis).

Cream Formulations

• Offer similar benefits to gels: control, slower penetration, and ease of visualization.
• Typically an oil-in-water emulsion.

Powder Formulations

• Mixed with water or activators (e.g., polyethylene glycol) to form a paste.
• Tend to have a heavier consistency than creams.
• May require longer application times due to slower partitioning of the active ingredient.
• Offer benefits such as stability (longer shelf life) and customization.
• Mixing the powder with a liquid is a good way to offer a customized appeal.

Influence of the base or solvent itself.

• The base formulation influences the penetration of substances.
• Penetration enhancers may be included to dissolve or alter the lipid bilayers of the skin, interact with keratin, modify desmosomes, alter metabolic activity, and enhance passive diffusion.
• Common penetration enhancers include:
  • Alcohol (ethanol): Dissolves lipid bilayers.
  • Water and humectants: Hydrate the stratum corneum for better transdermal delivery.
  • Surfactants: Soap-like molecules that disrupt lipids.

Alpha Hydroxy Acids (AHAs) and Beta Hydroxy Acids (BHAs)

AHAs Overview

• Most common peeling agents in clinical practice.
• Often called lunchtime peels due to superficial action, minimal visual impact, and quick recovery.
• Target the epidermis, with direct actions on different layers depending on peel strength.
• Most peels are very superficial or superficial (even 70% glycolic acid).
• Medium-depth peels reach the lower layers of the epidermis.
• Peels can have indirect effects on the dermis.
• AHAs share a common formula with a hydroxyl unit and a carboxylic acid functional group, with variability in the "R" region.
• They are polar molecules, water-soluble, and participate in hydrogen bonding.
• Larger molecules are less polar.

Polyhydroxy Acids (PHAs)

• Tend to be slightly less soluble in water and more soluble in alcohols (more non-polar).
• AHAs and PHAs have carboxylic acid functional groups.
• The "alpha hydroxy" name refers to the hydroxyl group being present on the carbon away from the acid group (the alpha carbon).

Time Dependence and Neutralization

• AHAs are time-dependent peels; duration on the skin determines the peeling action.
• They require neutralization to prevent ongoing skin damage; they do not self-neutralize.
• Peels are often partially neutralized for safety.
• Neutralization involves applying a base (e.g., bicarbonate solution) to form carboxylate salts and return the pH to neutral.
• AHAs have a good safety profile and can be considered non-toxic.

Types of AHAs

• Glycolic acid
• Lactic acid
• Malic acid
• Tartaric acid
• Citric acid
• Mandelic acid
• Mifitic acid
• These acids have slightly different molecular weights and properties.
• Glycolic acid is the simplest AHA with a small molecular weight, allowing easy penetration, and can be quite irritating.

Clinical Indicators for AHA Use

• Dry, barrier-disrupted skin
• Dyschromia/hyperpigmentation
• Rough, dry texture
• Acne (hyperkeratinization around hair follicles)

Glycolic Acid Regulation

• Glycolic acid is on the poison schedule.
• Classified as a metabolic agent at 30% free acid or below.
• Considered caustic (peeling agent) between 30-70%.

Mechanisms of Action of AHAs

• Often referred to as corroborrheic substances, but at superficial levels, they have a desmolytic action.
• Disrupt desmosome bonds between corneocytes rather than breaking apart keratin.
• The low pH reduces adhesion at cell-to-cell junctions, interfering with hydrogen ionic bonding within the corneal desmosome structure.
• Inhibits enzymes like kinases, sulfotransferases, and phosphotransferases, which attach sulfate and phosphate groups to corneocytes for desmosome formation.
• Activates proteases to break intercellular bonds.
• At lower concentrations, action is in the stratum corneum; at higher concentrations, it can reach the stratum granulosum.

Epidermolysis

• At higher concentrations, AHAs can cause epidermolysis, with effects down to the basement membrane.
• This induces desquamation, stimulating cell replacement.
• The skin detects cell loss and adjusts turnover to replace cells from below.
• Barrier function is typically restored within 24-48 hours due to the higher turnover rate.

Epidermal Thickening

• Results in a thickening of the stratum corneum and overall epidermis.
• Leads to a more ordered epidermal structure with fewer atypical cells.
• Quicker turnover allows for better barrier function to be reformed.
• Promotes orderly desquamation, with or without visible shedding.
• Beneficial in acne skins to reduce comedone formation.

Cellular Apoptosis and Other Effects

• Some studies show AHAs (citric and malic acid) can stimulate cellular apoptosis.
• They can trigger the production of caspases and induce the formation of reactive oxygen species, leading to cell cycle arrest and apoptosis.
• The stimulus from surface action makes the basal layer more mitotically active through cell signaling.
• Even superficial wounds upregulate transforming growth factor beta production, increasing epidermal cell turnover.

Pigment Dispersion

• Desquamation helps disperse pigment collecting in corneocytes on the skin's surface.

Humectant Effect

• AHAs can bond water as a humectant, especially at lower concentrations (10% or below).
• At these concentrations, they have more of a hydrating effect, rather than a peeling effect.
• Natural moisturizing factors include lactic acid, which is an AHA that holds onto water.
• Humectancy reduces transepidermal water loss, increases hydration, and makes the skin more pliable.

Enhancement of Peeling Action

• Having more water present helps indirectly with enhancing desquamation, as water is necessary for hydrolysis in the breakdown of proteins.
• Hydrating ingredients help provide water for this process.
• Higher concentrations of AHAs consumed water in the hydrolysis process that is needed for shedding, which can leave the skin more dehydrated afterward.

Dermal Effects

• The release of transforming growth factor beta can affect responses in the dermis.
• Stimulation of collagen production, improved collagen density, improved dermal structure and denseness, quality of elastic fibers, and glycosaminoglycans deposition.
• More significant effects are seen with concentration that are above 40% particularly with glycolic acid.

Antimicrobial Action and Angiogenesis

• Some studies show a mild antimicrobial action by adjusting skin pH.
• AHAs may help reduce microbial growth of non-normal flora pathogens.
• There may be a potential for stimulating the formation of new blood vessels (angiogenesis) via vascular endothelial growth factor signaling.
• Angiogenesis enhances wound healing and benefits vascular conditions like rosacea or older skins.

Concentration and Treatment Depths

• 10% or below: humectant function
• 20-30%: superficial light peels, breaking desmosome bonds in the stratum corneum
• Superficial peels may extend to the stratum granulosum and have dermal effects
• Higher concentrations: medium-depth peels, epidermolytic or keratolytic (deeper peeling)

Risk Management

• Base practice on the ability to manage complications.
• Start with lower percentages or milder peeling agents, and also ensure you have done a consultation from the client.
• Peels need to be neutralized.
• Foaming reactions can occur during neutralization and an exothermic reaction will cause a change in temperature.
• Partial or total neutralization can reduce the risk of complications.
• AHAs are delivered in progressive courses of treatments rather than one deep peel.
• If frosting or blanching occurs, epidermolysis is likely to have occurred, and the peel should be neutralized immediately.
• Part of the consultation process should include discontinuing retinoid use to prevent increased deep appealing from the product.
• Sometimes epidermolysis is necessary to rewound skin and improve it, particularly if it is scared.

Free Acids and Other Considerations

• Partially neutralized formulas of higher concentration may be enough to get that indirect stimulating effect.
• Lower pH leads to a more inflammatory response; higher pH creates a more hydrating response.
• If the pH of the solution is greater than the pKa, it tends to be more moisturizing; if it's less or equal to the pKa, it's a peeling agent.
• Maintenance is necessary.
• Most AHAs are synthetically derived for consistency.

Polyhydroxyacids (PHAs) and Alpha Ketonehydroxyacids

• These are slightly related compounds that have the same structure that we're staring to see more.
• PHAs have slightly different alpha chain and is much larger.
• PHAs tend to penetrate more slowly, and they are a lot less irritating than traditional AHAs so they can often be used on more sensitive skin.

Beta Hydroxy Acids (BHAs)

BHA Structure

• Carboxylic acid functional group.
• Longer hydrocarbon chain.
• Hydroxyl group attached to the carbon away from the carboxylic acid (beta position).
• Examples: salicylic acid, beta hydroxybutynoic acid, tropic acid, and trethanoic acid.
• Only salicylic acid is used for skin peeling.
• BHA is synonymous with salicylic acid.

Salicylic Acid Structure and Properties

• Benzene ring base (phenol base) with an alcohol functional group.
• Classified as a beta hydroxy acid.
• Larger molecule than AHAs with a big non-polar hydrocarbon area.
• Lipophilic and soluble in alcohol or ethanol, acetone, and polyethylene glycol, but only slightly in water.
• Often seen as a powder dissolved in an ethanol base for dissolving and penetration enhancement.
• Polyethylene glycol gel-type bases are also used to avoid pseudo-frosting.
• Has lowered stability in sunlight, so it is often in a powder form that is mixed later on.

Sources of Salicylic Acid

• Can be obtained from willow tree bark, sweet birch bark, and wintergreen.
• Most common source is synthetic, made by reacting carbon dioxide and phenylate together under pressure.

Salicylic Acid and Aspirin

• Closely related to aspirin (anti-inflammatory drug).
• Has anti-inflammatory properties and can have slight numbing/pain relief effects.
• Has good penetrative ability due to being non-polar.
• Goes into non-polar regions in the intercellular route more easily than more polar molecules.
• Penetrates via intercellular transcellular route and also through appendages like hair follicles that are very lipidic.

Mechanism of Action of Salicylic Acid

• Disrupts covalent bonding between lipid bilayers and the cornified envelope, rather than at desmosomes.
• Interferes with the desmosomes and corneal desmosomes by altering proteins within that.
• Triggers detachment and desquamation.
• Maximum effect is down to the basal layer, never further than that.
• Leaves the stratum corneum thinned.
• Has the same cell signaling pathway that leads to proliferation in deeper layers and increases cell turnover.
• Reduces surface pigment.

Acne Effects

• Desquamation within the pilosebaceous unit due to a lipid-rich environment.
• Can have a sebum-suppressive action.
• Oily parts of the skin might show more dramatic peeling.

Anti-inflammatory and Antimicrobial Actions

• Anti-inflammatory is the same pathway as aspirin.
• It modulates or inhibits cyclooxygenase activities, reducing prostaglandin production.
• That result leads to an anesthetic effect.
• Antimicrobial is mainly down to the acidic environment that it creates that's inhospitable to a lot of microbes.
• Changes some of those factors that are produced by the skin that are necessary for bacterial replication.

Dermal Components

• Cell signaling reaction.
• There is peeling on the epidermis but the cell signaling via transforming growth factor beta is increasing collagen synthesis and rearrangement of dermal components.
• Facilitates penetration of other products too.
• Disrupts the lipid bilayers, it makes it beneficial for enhanced delivery of other substances that might want to penetrate through to.

Clinical Indications

• Acne, oily skin, hyperpigmentation conditions, photo damage.
• Cautious use in darker Fitzpatrick skin types.
• Papular pustular rosacea benefits, and it also benefits the same lesions that we see in the case of acne.
• Fine lines, hyperkeratotic disorders, uneven texture.
• Most people can benefit from it in some way, shape, or form.

Salicylate Hypersensitivities and Cautions

• Some people are aware that they cannot take salicylates in tablets (e.g., aspirin).
• Not a procedure that is done in pregnancy.
• Contraindicated for clients on anticoagulant therapy (warfarin) due to increased risk of bleeding.
• High levels of salicylates are removed from the body via the kidneys or liver, so dysfunctions of those organs should indicate that people are not having the procedure.
• Barrier disruption already might deliver a greater dose than is originally intended.

Application Techniques

• Applied in coats rather than a time-dependent manner.
• Layering and coating the skin in a methodical manner is absolutely the key to it.
• Don't want to overlap at all.
• Need to have a methodical sectioning off of the skin and make sure that you're applying it in that very even way so that you don't have the overlap or any pooling in areas.
• Initial heat and burning stinging sensations are quite normal, but then usually within a minute or so, you'll get that numbing effect and so that actually helps a little bit with reducing that burning stinging sensation.

Peeling and Frosting

• Peeling is often much more noticeable for these sorts of appeals. Particularly if you've got areas that are oilier, you might be seeing a bit more peeling in the subsequent days.
• White precipitation is giving giving you that pseudo frosting that's occurred due to the evaporation of the alcohol.
• True frosting, is more like you've obviously got a darker Fitzpatrick skin type and this sort of blanching particularly around those lesions there which are a little bit earlier, acne time lesions. And you can see the areas of necrosis occurring.
• Do proceed with caution when delivering this formula type appeal on individuals with darker Fitzpatrick skin types.
• Polyethylene glycol is slowing down the delivery of the formula and tends to then not get that pseudo frosting occurring.

Polyethylene Glycol Based Formulas

• Polyethylene glycol is often left on for about 5 minutes and then removed with water.
• The reason you're moving with water is it's a gel base and it's quite occlusive to the skin, so it feels sticky like you've got a film on the surface of your skin.
• The removal of excess formula from the skin will offer a less obvious feeling in these cases.
• Usually removed with treatment after that gel formula is added.
• Any white appearance on inflammatory lesions might indicate echodermolysis of those areas.

Course of Treatments and Maintenance

• Course of treatments is required. So we usually repeat every two to four weeks, do three to six treatments is fairly common treatment regimes.
• They don't need to be peeled. They tend to give quite a superficial peeling effect at those lower concentrations.
• Higher concentrations in cream base can be used for actinic damage or some related damage. particularly that on the hands.
• High concentrations of salicylic acid on hand and hand and body products that are formulated to reduce calluses on the feet.

Systemic Absorption and Toxicity

• Can be absorbed into the systemic circulation; caution with liver or kidney problems.
• Procedure doesn't significantly change excretory pathways, but we need to be careful with people who have salicylism.
• Salicylism is that toxicity leading to rapid breathing, ringing in the ears, hearing loss, dizziness, nausea, vomiting, etcetera.
• Studies looking at circulating levels of salicylate during peels show actually very, very low levels- well below any toxicity.
• Biggest risk with any of this is- large part of your body being peeled or you're applying that product or higher concentration over a large portion of the body to older people or who is at more risk. But usually twenty four to seventy two hours after the cessation, even if you get these symptoms of salicylism, you should see these symptoms reduce.

Contact Sensitization and Allergic Contact Dermatitis

• Some people might be able to contact sensitization and might develop in allergic contact dermatitis, but because of a hot wire rate. So again, this can be particularly careful and that don't eat is don't drink it.

Lipohydroxy Acids

• Related new compound similar to the Polyhydroxyacids
• A derivative of salicylic acid with a long hydrocarbon chain (very lipophilic/non-polar).
• Large molecular size reduces penetration, leading to a slower, less irritant peeling reaction.
• Targets individual coroneocytes, rather than bulk peeling of the skin through the effects of saliva acid at higher concentrations.

Key Considerations for Peeling Effect

• Type of peeling agent
• Concentration
• Duration of contact (for time-dependent peels)
• Levels of layers (for BHA peels)
• pH and pKa
• Quantity applied
• Application technique
• Skin condition and where you're applying the peel
• Combinations of peeling agents are often used to give the treatment effect or greater treatment as concentrations the other key concepts to consider.
• Combinations of peeling agents are often used for better treatment effect or depth of penetration. Example: Jessner solution which usually requires dramatic pills.

Free Acid

• Free acid refers to what's bioavailable to dissociate once it penetrates the skin.
• Once ionized or dissociated, the penetration slows down. Free acid penetrates much more frequently, but as soon as it's been dissociated or ionized, that then stops it penetrating at that particular point.

Application Techniques and Skin Preparation

• Rub the peeling area rather than simply putting the peeling on the skin for peeling purposes.
• Preparing the skin beforehand- skin stripping during clinical cleanse that degreasing skin with chemicals to give us a chance to let the peeling get into the skin.

Anatomical Location and Skin Characteristics

• Oily thickened skin reduces the peeling action unless using salicylic acid.
• Thin dry skin increases the peeling action.
• The face is thinner than the torso, allowing deeper penetration, but the face has more pilosebaceous units and sweat glands, leading to quicker responses and epidermal regeneration.
• Cannot do very deep peels on many other areas in the body other that the face simply through a lack of the gland availability.