Can Azelaic Acid Revolutionize Dermatology, From Acne to Skin Cancer?

🔍 Key Finding Liposomal formulations of azelaic acid (AZA) show enhanced skin penetration and accumulation in the stratum corneum compared to standard formulations, suggesting improved bioavailability and potential for optimizing dermatological treatments. This is particularly promising for skin cancer treatment, where poor skin absorption has limited AZA’s therapeutic use.

🔬 Methodology Overview

• Design: Narrative review.
• Data Sources: Published literature.
• Scope: Azelaic acid’s mechanism of action, pharmacokinetics, dermatological applications, and potential use in skin cancer therapy, including a review of available formulations and liposomal technology.
• Analysis Approach: Qualitative synthesis of findings from in vitro and in vivo studies, clinical trials, and case reports. Discussion of liposomal technology’s advantages and limitations in drug delivery, specifically regarding azelaic acid.

📊 Results

• Rosacea: In a study of 961 patients, 15% azelaic acid (AZA) foam was more effective than placebo (32.0% vs. 23.5%; p < 0.001). 15% AZA gel was also more effective than 0.75% and 1% metronidazole gel in separate studies.
• Acne vulgaris: 20% AZA cream was as effective as 0.05% tretinoin cream for comedonal acne, with fewer side effects. 15% AZA was more effective than 0.1% adapalene gel for inflammatory lesions in a 9-month study.
• Melasma: 20% AZA cream and 2% hydroquinone cream showed similar efficacy in reducing pigment intensity and lesion size in one study. Another study found 73% of patients using 20% AZA cream saw beneficial effects compared to 19% using 2% hydroquinone. Combining 20% AZA with 5% hydroquinone showed faster results than 5% hydroquinone alone, but with more side effects.
• Follicular Keratosis: 92% of skin treated with 20% AZA cream improved compared to 83% treated with Cetaphil cream.
• Male Pattern Baldness: A combination of 5% minoxidil, 1.5% AZA, and 0.01% tretinoin was as effective as 5% minoxidil alone for hair growth and thickening.
• Liposomal AZA: Liposomal AZA gel showed higher AZA concentration in the stratum corneum compared to non-liposomal formulations in a Franz cell diffusion study, suggesting improved bioavailability. A 10% liposomal AZA gel achieved high stratum corneum accumulation (187.5 µg/cm²) and strong antimicrobial activity without preservatives.
• Skin Cancer (Preliminary): Topical and oral AZA showed arrest and regression of malignant melanoma lesions in a small study of 23 patients. Topical AZA led to complete resolution of lentigo maligna in >50 patients in another study, with long-lasting results (5-10 years disease-free). However, other studies showed limited or mixed results, and some cases of progression to invasive melanoma during treatment were reported. More research is needed.

💡 Clinical Impact Topical azelaic acid is effective in treating various dermatoses, including acne, rosacea, and hyperpigmentation, and liposomal formulations enhance skin penetration and bioavailability, potentially optimizing treatment and reducing the required API concentration. While not currently standard practice, azelaic acid has shown promise in treating some skin cancers and warrants further investigation as a potential therapeutic option.

🤔 Limitations

• Poor absorption through the skin with conventional formulations necessitates repeated applications for sustained efficacy.
• Side effects such as local skin irritation (tingling, redness) can occur.
• Liposomal formulations can potentially induce complement activation-related pseudoallergy (CARPA) in susceptible individuals.
• Limited research exists on AZA’s use in skin cancer treatment, requiring caution.
• Combining AZA with other treatments like hydroquinone or glycolic acid may increase side effects despite potentially enhanced efficacy.
• Studies on AZA for conditions like male pattern baldness and follicular keratosis show limited or no significant advantage over existing treatments.
• Long-term effects of liposomal AZA formulations require further investigation.

✨ What It Means For You This research suggests that liposomal azelaic acid formulations may offer enhanced penetration and bioavailability compared to traditional creams and gels, potentially improving treatment outcomes for various dermatological conditions like acne, rosacea, and melasma. Doctors should consider liposomal AZA as a potential therapeutic option, especially in cases where conventional AZA formulations have proven ineffective or are poorly tolerated, while remaining aware of the limited research on its use in skin cancer.

Reference Sauer N, Oślizło M, Brzostek M, Wolska J, Lubaszka K, Karłowicz-Bodalska K. The multiple uses of azelaic acid in dermatology: mechanism of action, preparations, and potential therapeutic applications. Adv Dermatol Allergol. 2023;40:716-724. https://doi.org/10.5114/ada.2023.133955