Ultradeformable Vesicle-Loaded Smart Gels for Enhanced Ocular Bioavailability

Abstract

Ocular drug delivery systems face significant challenges due to the physiological and anatomical barriers of the eyes. Nanotechnology has emerged as a promising approach to overcome these limitations and potentially improve ocular bioavailability and patient compliance. Lipid-based ultra-deformable vesicular systems have garnered considerable attention due to their unique ability to permeate the ocular barriers. These systems are further optimized with edge activators and mucoadhesive properties to enhance drug retention at the ocular surface and reduce the frequency of dosing. An integrative strategy combining deformable vesicles with in situ gels has demonstrated augmented therapeutic efficacy by improving penetration, prolonging retention, and sustaining drug release. Preclinical studies have demonstrated promise for treating several anteriorand posterior-segment ocular diseases; however, translating these technologies to clinical applications faces challenges in terms of scalability, reproducibility, and safety. The lack of comprehensive toxicity studies and animal models that mimic the human ocular anatomy and physiology hinders progress. This review provides insights into the advancement of ultra-deformable vesicles loaded with in situ gels for the treatment of various diseases in ocular drug delivery. Furthermore, the challenges associated with translating these technologies into clinical applications have been discussed.