Cannabidiol-Loaded Hyaluronic Acid-Based Nanogel for Inflammatory Acne: In Vitro and Open-Label, Non-Randomized Clinical Evaluation of Efficacy and Tolerability

Acne is a common inflammatory skin condition that significantly impacts quality of life. Standard treatments often cause skin irritation or contribute to antibiotic resistance. Cannabidiol (CBD) has demonstrated anti-inflammatory and sebum-regulating properties; however, its application is limited by poor solubility and stability. This study investigated the physicochemical properties of a CBD-loaded hyaluronic acid–graft-poly(N-isopropylacrylamide) nanogel (Hy-CBD). The biological activities of Hy-CBD, including its anti-inflammatory and antioxidant effects, were also evaluated. In addition, an exploratory clinical study was conducted to assess the safety and efficacy of the formulation in 22 Asian participants with inflammatory acne. In this open-label, non-randomized study, participants applied the gel twice daily for seven days. Assessments of skin tolerance, lesion size, redness, and pigmentation were performed at baseline, Day 2, and Day 7 using clinical examination and imaging analysis. The Hy-CBD gel was clinically tolerated, with no evidence of comedogenic or acnegenic potential. By Day 7, inflammatory lesion size was reduced by 46%, with significant improvements in redness and post-inflammatory pigmentation. All participants reported a subjective reduction in acne severity and expressed satisfaction with the treatment outcomes. These findings suggest that the Hy-CBD gel is a safe and promising delivery system for acne management. Nevertheless, larger randomized controlled studies are required to validate these preliminary findings.