Objective <p>The objective of this study was to develop and evaluate a crisaborole-loaded niosomal gel for enhanced topical delivery in the management of atopic dermatitis (AD), aiming to improve skin penetration, sustain drug release, and enhance therapeutic efficacy compared to conventional topical formulations.</p> Methods <p>Crisaborole-loaded niosomes were prepared using the thin-film hydration technique with Tween 80 as the surfactant and cholesterol as the stabilizing agent. The formulated niosomes were characterized for vesicle size, polydispersity index, zeta potential, encapsulation efficiency, and physical stability. The optimized niosomal suspension was subsequently incorporated into a Carbopol-based gel. The resulting niosomal gel was evaluated for physicochemical properties including pH, viscosity, spreadability, drug content uniformity, and in vitro drug release behavior.</p> Results <p>The optimized niosomal formulation exhibited nanoscale vesicle size, high encapsulation efficiency, and satisfactory colloidal stability. Incorporation into the Carbopol gel resulted in a smooth, homogenous formulation with skin-compatible pH and good spreadability. In vitro release studies demonstrated a controlled and sustained release profile of crisaborole from the niosomal gel compared to conventional formulations, indicating improved drug retention and prolonged availability at the site of application.</p> Conclusion <p>The developed crisaborole-loaded niosomal gel represents a promising topical drug delivery system for the treatment of atopic dermatitis. By enhancing skin penetration and providing sustained drug release, this formulation has the potential to improve therapeutic outcomes and patient compliance. The niosomal gel system offers a well-tolerated and effective platform, positioning it as a next-generation topical treatment for inflammatory skin disorders such as AD.The developed crisaborole-loaded niosomal gel represents a promising topical drug delivery system for the treatment of atopic dermatitis. By enhancing skin penetration and providing sustained drug release, this formulation has the potential to improve therapeutic outcomes and patient compliance. The niosomal gel system offers a well-tolerated and effective platform, positioning it as a next-generation topical treatment for inflammatory skin disorders such as AD.</p> Graphical Abstract <p></p>