Brimonidine ocular hypotensive effect can be enhanced by increasing residence time and corneal penetration. The current work aimed to formulate, evaluate and compare nanostructured lipid carriers (NLCs) to solid lipid nanoparticles (SLNs) and commercial eye drops for controlled brimonidine delivery. NLCs prepared by modified high shear homogenisation were spherical with a mean size of 151.97 +/- 1.98nm, negative zeta potential (ZP) of -44.2 +/- 7.81mV, % entrapment efficiency (EE) of 83.631 +/- 0.495% and low crystallinity index (CI) (17.12%), indicating a better drug incorporation. Moreover, they kept stable during storage at 4 degrees C for 3months. Permeability coefficient of NLCs was 1.227 folds higher than that of SLNs. Histological examination revealed localisation of NLCs in the anterior ocular chamber. NLCs revealed the most sustained and highest intraocular pressure (IOP) lowering activity (-13.14 +/- 1.28mmHg) in rabbits. In conclusion, NLCs is a promising approach for IOP reduction compared to eye drops and SLNs.