Smart lipid-based nanocarrier system for the topical delivery of ocular therapeutics bio-interfacing, physicochemical diversity, and routing barriers.

Delivering the drug to the eye using topical delivery poses significant challenges, owing to precorneal obstacles, rapid clearance mechanisms, and adverse bioavailability. The recent development of smart lipid-based nanocarriers, including solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs), liposomes, nanoemulsions, and micelles, has demonstrated the capability to address these limitations by increasing mucoadhesion, slowing release, and facilitating penetration of drugs through the epithelial lining. The review examines the categorisation, design concepts, and bio-interfacing strategies of the lipid-based delivery system used in the ocular application. This review focuses on the physicochemical diversity and the capability of traversing the ocular barriers. Several formulations exhibit promising translational applicability, including chitosan-coated SLNs of ofloxacin, which increased transcorneal permeation as compared to commercial drops, and NLCs containing diosmin, which exhibited anti-inflammatory activity and cytocompatibility in vitro tests against retinal cells. In vivo, ripasudil in liposomes protected fibrosis in the subretinal layer, and NLCs of ciprofloxacin and natamycin enhanced antimicrobial activity with a dual drug combination. Stimuli-responsive systems, such as temperature-sensitive and pH-sensitive hydrogels, offer prolonged ocular residence time and site-specific delivery in the eye. Preclinical studies also support the potential application of SLNs of bimatoprost in the long-term reduction of intraocular pressure and PEGylated NLC in protein delivery in posterior segment diseases. The review has also discussed formulation scalability, toxicity, and regulatory barrier problems, and it also explores future integration with personalised medicine and non-invasive delivery platforms.