Cubosomes as advanced nanocarriers for glaucoma therapy: A comprehensive review

Glaucoma is a chronic, progressive optic neuropathy and a leading cause of irreversible blindness worldwide, primarily managed through long-Term Intraocular Pressure (IOP) reduction. Conventional ocular drug delivery systems, particularly topical eye drops, suffer from poor bioavailability, rapid precorneal elimination, limited corneal permeability, frequent dosing requirements, and poor patient compliance, ultimately compromising therapeutic efficacy. In recent years, nanotechnology-based delivery systems have emerged as promising strategies to overcome these limitations. Among them, cubosomes nanoscale dispersions of bicontinuous cubic liquid crystalline phases have gained increasing attention as advanced ocular nanocarriers. Owing to their unique internal nanostructure, high surface area, and dual aqueous-lipid domains, cubosomes enable efficient encapsulation of hydrophilic and lipophilic drugs, sustained and controlled release, enhanced corneal permeation, prolonged ocular residence, and reduced systemic exposure. This review provides a comprehensive overview of the pathophysiology and current treatment limitations of glaucoma, structural and physicochemical characteristics of cubosomes, formulation and preparation strategies, mechanisms by which cubosomes enhance ocular drug delivery, and their specific advantages in glaucoma therapy. Recent advances in cubosome-based antiglaucoma formulations, challenges in manufacturing and clinical translation, regulatory considerations, and future perspectives are critically discussed. Collectively, cubosomes represent a highly promising nanocarrier platform with the potential to significantly improve therapeutic outcomes and patient adherence in long-term glaucoma management.