**Background:** The eye's anatomical barriers (tear film, cornea, blood-ocular barriers) limit topical drug penetration, residence time, and bioavailability, often requiring frequent high-dose administrations that reduce compliance and increase side effects. Polymeric nano-based drug-delivery systems (DDS) offer a solution by using biodegradable, nano-sized carriers that can traverse these barriers, provide sustained release, and target specific tissues. This review provides a comprehensive overview of polymeric nano-based DDS for anterior segment diseases and glaucoma, covering material science, preclinical and clinical studies from 2017 to 2022.
**Methods:** The authors conducted a literature review of preclinical and clinical studies published between 2017 and 2022, focusing on polymeric nano-based DDS for ocular diseases. They examined various biopolymers (hyaluronic acid, cellulose, chitosan, alginate, PLGA, poloxamers, cyclodextrins) and DDS types (nanomicelles, liposomes, nanoparticles, dendrimers, hydrogels, nanosuspensions, nanoemulsions, microneedles). The review also discusses anatomical and physiological factors affecting ocular drug delivery and summarizes studies on glaucoma (IOP-lowering and neuroprotection) and anterior segment diseases (dry eye, meibomian gland dysfunction, conjunctivitis, keratoconus, keratitis, cataracts).
**Key Results:** For glaucoma, preclinical studies showed that PLGA nanoparticles with brinzolamide significantly reduced IOP in animal models with minimal toxicity (Song et al., 2020; Salama et al., 2017). Chitosan nanoparticles (28±5 nm) delivered brimonidine via receptor-mediated endocytosis (Barwar et al., 2019). A Phase 2 study of a bimatoprost chitosan-based insert (Rubiao et al., 2021) in 16 POAG and 13 ocular hypertension patients achieved 30% IOP reduction by week 3 vs. 35% with drops, with no major side effects. The FDA-approved Durysta implant (bimatoprost, PLGA/poly-lactic acid) showed non-inferiority to timolol in Phase 3 trials (2020). For dry eye, Cequa (cyclosporine A nanomicelles) increased tear production and improved ocular surface integrity after 84 days (Phase 3). KPI-121 (loteprednol etabonate nanosuspension, ~300 nm) achieved threefold higher ocular exposure than conventional formulation in rabbits and reduced dry eye signs in ~2700 patients (Phase 3). For keratitis, a ganciclovir gel (sodium hydroxide, mannitol, benzalkonium chloride) is the only approved polymeric DDS, requiring five times daily application. Preclinical studies for cataracts showed PLGA-curcumin/cerium oxide nanoparticles protected lens epithelial cells with lower toxicity than subcutaneous injections (Liu et al.).
**Clinical Implications:** Polymeric nano-based DDS offer significant advantages: improved bioavailability, sustained release (reducing dosing frequency), targeted delivery, and biodegradability (minimizing toxicity). For glaucoma, these systems can enhance IOP control and patient adherence, with Durysta and chitosan inserts already in clinical use. For anterior segment diseases, nanoemulsions and nanomicelles (e.g., Restasis, Cequa) are standard for dry eye, while novel systems for keratitis and cataracts are in preclinical stages. Challenges include variability in biodegradation (e.g., Durysta), potential systemic absorption (e.g., LAPONITE-brimonidine in rats), and need for long-term safety data. Future research should focus on optimizing polymer combinations, improving stability, and translating neuroprotective strategies to clinical settings.