Formulation and Evaluation of Niosome-Based Isotretinoin Gel: A Comprehensive Review

Acne vulgaris is a chronic inflammatory disorder of the pilosebaceous unit affecting millions of adolescents and adults worldwide. Although isotretinoin remains one of the most effective retinoids for acne management, its conventional topical formulations are associated with poor aqueous solubility, limited skin penetration, photo-instability, irritation, erythema, and reduced patient compliance. Nano-vesicular drug delivery systems have emerged as promising alternatives to overcome these limitations. Among them, niosomes have attracted considerable attention owing to their excellent biocompatibility, chemical stability, ease of preparation, cost-effectiveness and ability to encapsulate both hydrophilic and lipophilic therapeutic agents. Incorporation of isotretinoin into niosomal vesicles followed by dispersion in a topical gel provides controlled drug release, enhanced skin retention, improved follicular targeting, reduced systemic absorption and minimized local adverse effects while maintaining therapeutic efficacy. This review comprehensively discusses the pharmaceutical aspects of isotretinoin-loaded niosomal gels, including formulation strategies, selection of surfactants and membrane stabilizers, methods of niosome preparation, vesicle characterization, gel formulation approaches, physicochemical evaluation, stability assessment and biological performance. Furthermore, recent advances in vesicular nanocarriers, quality-by-design approaches, optimization techniques and translational perspectives are highlighted. Current challenges related to large-scale manufacturing, regulatory considerations and clinical translation are also discussed. Overall, niosomal gel represents a promising topical delivery platform capable of improving the therapeutic performance of isotretinoin and may contribute to safer, more effective and patient-friendly acne treatment. Keywords: Isotretinoin, niosomes, topical gel, vesicular drug delivery, acne vulgaris