Proniosomal Gel in Ocular Drug Delivery: A Comprehensive Review of Recent Formulation Advances

Abstract

Ocular drug delivery remains one of the most formidable challenges in pharmaceutical sciences owing to the numerous anatomical, physiological, and dynamic barriers of the eye. Conventional ophthalmic formulations such as eye drops suffer from extremely poor bioavailability, typically less than 5%, primarily due to rapid nasolacrimal drainage, lacrimation, and the impermeability of the corneal epithelium. Proniosomal gels represent a novel, hybrid vesicular-gel system that combines the advantages of niosomes non-ionic surfactant-based vesicles with the sustained-release and mucoadhesive properties of hydrogels. In the proniosomal approach, a dry, carrier-coated lipid formulation is hydrated upon application to form niosomes in situ, thereby overcoming the physical instability associated with conventional niosomal dispersions. This review comprehensively examines the principles, composition, preparation methodologies, physicochemical characterization, and in vitro/in vivo performance of proniosomal gel systems reported in the literature between 2015 and 2025. Recent formulation studies encompassing anti-glaucoma agents (timolol maleate, brimonidine tartrate, latanoprost), anti-infective drugs (ciprofloxacin, voriconazole, natamycin), non-steroidal anti-inflammatory drugs (diclofenac sodium, ketorolac tromethamine), corticosteroids (prednisolone acetate, loteprednol etabonate), and immunosuppressants (cyclosporine A) are critically analysed. Key formulation variables, evaluation parameters, and pharmacokinetic/pharmacodynamic outcomes are discussed. Current challenges, regulatory considerations, and future directions, including stimuli-responsive and nanotechnology integrated proniosomal systems, are also highlighted.