This study examined whether borneol could enhance corneal drug permeability. Model drugs containing either synthetic or natural borneol were co-administered to isolated intact or de-epithelialized rabbit corneas and the apparent permeability coefficients were measured. Draize tests in rabbits and levels of isolated intact rabbit corneal hydration were used to measure in vivo and in vitro toxicity, respectively. Synthetic borneol (0.1%) increased corneal penetration of the lipophilic agents, indomethacin and dexamethasone, by 1.23 and 2.40, respectively, and of the hydrophilic agents, ofloxacin, ribavirin and tobramycin, by 1.87, 2.80 and 3.89, respectively. For natural borneol, the corresponding fold increases were 1.67, 2.00, 2.15, 2.18 and 3.39, respectively. Removing the epithelium attenuated the penetration-enhancing effects of borneol. Borneol (0.1%) did not damage corneal tissue. The ability of borneol to enhance drug penetration through the outer corneal layer, particularly for highlyhydrophilic drugs, suggests that further clinical investigation may be warranted.

Menthol may improve the ocular penetration of a drug in a transcorneal and transscleral drug delivery system without causing toxic reactions.

The aim of this study was to investigate the effect of two sperminated pullulans (SP) with a different number of amino groups (SP-L, amino group content 0.124 mmol/g polymer; and SP-H, amino group content 0.578 mmol/g polymer) on the permeation of drugs through isolated rabbit corneas. Determination of corneal hydration levels and Draize eye tests were performed to assess the safety of SP both in vitro and in vivo. For 0.2% (w/v) SP-L and 0.2% (w/v) SP-H, the enhancement ratios (ERs) with dexamethasone of 1.34 and 1.42, respectively, were not statistically significant. For ofloxacin, tobramycin and sodium fluorescein, the ERs with 0.2% SP-L were 1.37, 2.02 and 2.12, respectively, and with 0.2% SP-H the ERs were 1.84, 4.69 and 6.87, respectively; these ERs were all statistically significant. Enhancement increased with increasing amino group content of the SP. The improved transcorneal drug absorption via the paracellular route indicated opening of the tight junctions in the corneal epithelium. Irritation tests indicated that 0.2% SP-L and 0.2% SP-H did not damage the corneal tissues.