Poly(D,L-lactide-co-glycolide) nanospheres incorporating flurbiprofen were prepared by the solvent displacement technique for purposes of assessing (i) drug-polymer physicochemical interactions, (ii) flurbiprofen release from the polymer matrix and (iii) eye permeation of the drug formulated in the colloidal system. The resulting nanospheres were on average 200-300 nm in size and bore a negative charge (xi-potential around -25 mV). They were shown by atomic force microscopy and transmission electron microscopy to be spherical and regular in shape. Thermal methods, infrared spectroscopy and X-ray diffraction showed that the drug was dispersed inside the particles. These tests evidenced an eutectic mixture meaning more widespread dispersion of the drug in the polymer system. Entrapped flurbiprofen was released in vitro from the polymer system by dissolution and diffusion in high drug loaded nanospheres, whereas those with a lesser load showed only diffusion. The ex vivo corneal permeation study showed that flurbiprofen-loaded nanospheres enhanced drug penetration by about twofold over commercial eye drops containing poly(vinyl alcohol) and by about fourfold over flurbiprofen in pH 7.4 phosphate buffer. The corneal hydration level of each cornea was determined to evaluate potential corneal damage.