Quick Comparison

AdapaleneHyaluronic Acid
Typical ConcentrationOTC: 0.1% gel, apply pea-sized amount once nightly to clean, dry skin. Prescription: 0.3% gel for more resistant acne. Can be applied to slightly damp skin with less irritation than tretinoin. Results visible at 8-12 weeks.Concentrations: 0.1-2%. Higher is not always better — concentrations above 2% can feel sticky and may actually pull moisture FROM skin in dry climates. Multi-molecular weight formulations are preferred. Apply to damp skin and seal with moisturizer.
ApplicationTopical (gel, cream, lotion). More stable than tretinoin — can tolerate some benzoyl peroxide layering (Epiduo combines both).Topical (serum, cream, mask). Apply to damp skin and layer occlusive on top. Injectable HA fillers are a separate medical category.
Research Papers8 papers10 papers
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Mechanism of Action

Adapalene

Adapalene selectively binds RAR-beta and RAR-gamma (minimal RAR-alpha affinity), reducing inflammatory signaling compared to pan-RAR agonists. It normalizes follicular epithelial differentiation and reduces corneocyte cohesion in the pilosebaceous unit, preventing microcomedo formation. Adapalene inhibits AP-1 transcription factor (c-Fos/c-Jun dimerization), suppressing IL-6, TNF-alpha, and neutrophil chemotaxis. It promotes comedolysis by accelerating desquamation of existing comedones. For anti-aging, it stimulates fibroblast collagen I and III via RAR-beta/gamma, with comparable efficacy to tretinoin. Its lipophilic naphthoic acid structure confers superior follicular penetration and light stability.

Hyaluronic Acid

Hyaluronic acid is a glycosaminoglycan (GAG) composed of repeating D-glucuronic acid and N-acetyl-D-glucosamine disaccharides. Its hydroxyl and carboxyl groups create strong hydrogen bonding with water—each molecule binds up to 1000x its weight in water. High molecular weight HA (>1000 kDa) forms a viscoelastic film on the stratum corneum, reducing transepidermal water loss (TEWL). Medium weight (100-1000 kDa) penetrates the upper epidermis. Low molecular weight HA (<100 kDa) reaches the dermis and binds CD44 and RHAMM receptors on fibroblasts, triggering ERK and PI3K signaling that stimulates fibroblast proliferation, hyaluronan synthase (HAS2) expression, and collagen I/III synthesis. Sodium hyaluronate—the salt form—has improved stability and penetration. Multi-weight formulations provide surface hydration and deeper dermal stimulation.

Risks & Safety

Adapalene

Common

Dryness, peeling, redness — generally less than tretinoin. Initial purging for 4-6 weeks.

Serious

Avoid in pregnancy (retinoid class).

Rare

Allergic contact dermatitis, severe peeling.

Hyaluronic Acid

Common

Stickiness at high concentrations. In very dry/arid climates, HA can draw moisture from deeper skin layers to the surface where it evaporates.

Serious

None.

Rare

Mild irritation from very low molecular weight HA penetrating too deeply.

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