Nanotechnology-based non-invasive strategies in ocular therapeutics: Approaches, limitations to clinical translation, and safety concerns

The eye is a highly sensitive and vital component that significantly affects human quality of life. Diseases that affect the eye are major contributors to visual impairment and blindness and can have a profound effect on an individual's well-being. Ocular drug delivery is challenging because of physiological and anatomical barriers. Invasive Intravitreal administration is primarily used for the treatment and management of posterior segmental disease. However, frequent intravitreal administration is associated with adverse effects. Furthermore, topical administration results in less than 5% ocular bioavailability, leading to a void in the safe and efficacious management of posterior segment diseases. Nanocarrier-based systems have been well explored as ocular therapeutics to overcome the sub-therapeutic management attributed to conventional eye drops and physiological and anatomical barriers. Since the first report of nanoparticles to date, the nanocarrier system has come a long way with the simplicity and versatility offered by the system. Significant progress has been made in the development of noninvasive nanocarrier systems and their interactions with the ocular surface. The nanocarrier system enhances precorneal retention, limits nontherapeutic absorption, and offers controlled drug release. This review aims to provide an overview of the recent advancements in noninvasive nanocarrier-based topical ocular drug delivery systems, including their interaction with the ocular surface, the barriers to their translation to clinical settings, and the associated scale-up challenges.