Emerging drug delivery strategies for glaucoma therapy: focus on nanoparticles and stimuli-responsive systems

Abstract

Glaucoma is a progressive and chronic eye complication characterized by elevated intraocular pressure (IOP) and consequential optic nerve damage, ultimately leading to blindness. Current therapeutic interventions mainly focus on frequent topical administration of IOP-lowering agents. However, ocular tissues cause prompt clearance of the administered drugs, thereby leading to low bioavailability and reduced patient compliance. This necessitates the development of advanced delivery systems that not only enhance the ocular residence of therapeutic agents but also govern drug release at the site of interest in a spatiotemporally controlled manner. The emergence of nanomedicine and stimuli-responsive delivery systems partially helped to achieve these objectives. These systems show improved permeability, longer ocular retention, or stimuli-responsive drug release (against specific triggers like temperature, pH, ion or enzymes), thereby offering on-demand drug release at the site of interest. This review discusses the anatomy and physiology of ocular tissues, emphasizing their barrier properties for drug delivery in glaucoma therapy. The challenges associated with conventional drug delivery approaches, routes of drug administration, and the need for the development of advanced drug delivery systems have also been emphasized. Furthermore, recent advances in the development of polymeric ophthalmic drug delivery systems and formulation strategies are mentioned with a special emphasis on nanoparticles, in situ gels, and stimuli-responsive systems. Finally, we present our perspectives on scale-up issues, regulatory hurdles, and clinical translation of advanced drug delivery systems.