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Acne vulgaris is a common dermatologic disorder that affects approximately 85% of teenagers, which significantly impacts the quality of life in adolescents. It is a chronic disease of the sebaceous follicles that is multifactorial in etiology. Topical treatment is the first choice for mild and moderate acne, while systemic therapy is reserved for severe and certain moderate cases. Topical treatments include retinoids (e.g., tretinoin and adapalene), antibiotics (e.g., clindamycine), and other agents (e.g., benzoyl peroxide and azelaic acid), often applied in combination. The mechanisms of action include antimicrobial, anti-inflammatory, and keratolytic activities, as well as sebum secretion reduction, and the normalization of follicular keratinization. However, these topical agents commonly induce side effects, such as dryness, burning, stinging, peeling, redness, erythema, and photosensitivity. Therefore, there is a need to reduce the side effects of anti-acne drugs, while maintaining or enhancing their therapeutic effectiveness. This article aims to comprehensively outline nanotechnology strategies, particularly the use of phospholipid-based nanocarriers like liposomes and related vesicles, to enhance therapeutic efficacy, skin tolerability, and patient compliance in the treatment of acne vulgaris. In addition, novel active ingredients encapsulated in vesicles beyond those recommended in official guidelines are discussed. © 2024 by the authors.