OBJECTIVE: To explore the use of oleic acid (OA) in ocular drug delivery. METHODS: Six compounds, namely rhodamine B, sodium-fluorescein, fluorescein isothiocyanate (FITC) dextrans of 4, 10, 20 and 40 kDa were selected as model drugs. The effect of OA on the corneal permeability of drugs was evaluated in vitro, using isolated rabbit corneas by a Franz diffusion cell. The safety of OA was assessed on the basis of corneal hydration level. The ocular irritation of OA was also tested in rabbits in vivo using the Draize eye test. RESULTS: In the presence of OA, at a concentration of 0.02-0.1%, the maximum increase in the apparent permeability coefficient (Papp) was 3.21-, 1.76- and 1.57-fold for rhodamine B, sodium-fluorescein and FITC-dextran of 4 kDa, respectively. However, no significant permeability enhancement of FITC-dextrans of 4, 10, 20 and 40 kDa was found in the presence of OA. It enhanced the corneal penetration of model compounds in a concentration-dependent manner. The Papp values of rhodamine B decreased with increasing concentration of OA, while the Papp values of sodium-fluorescein and FITC-dextrans of 4 kDa increased. The Papp enhanced by 0.1% OA was logarithmically correlated to the molecular weight of model drugs (R(2) = 0.9991). With the 0.02%, 0.05% and 0.1% oleic application, the corneal hydration values were <83%, and Draize scores were <4. CONCLUSION: OA may have potential clinical benefits in improving the ocular drug delivery of both hydrophilic and lipophilic compounds.
OBJECTIVE: To explore the use of oleic acid (OA) in ocular drug delivery. METHODS: Six compounds, namely rhodamine B, sodium-fluorescein, fluorescein isothiocyanate (FITC) dextrans of 4, 10, 20 and 40 kDa were selected as model drugs. The effect of OA on the corneal permeability of drugs was evaluated in vitro, using isolated rabbit corneas by a Franz diffusion cell. The safety of OA was assessed on the basis of corneal hydration level. The ocular irritation of OA was also tested in rabbits in vivo using the Draize eye test. RESULTS: In the presence of OA, at a concentration of 0.02-0.1%, the maximum increase in the apparent permeability coefficient (Papp) was 3.21-, 1.76- and 1.57-fold for rhodamine B, sodium-fluorescein and FITC-dextran of 4 kDa, respectively. However, no significant permeability enhancement of FITC-dextrans of 4, 10, 20 and 40 kDa was found in the presence of OA. It enhanced the corneal penetration of model compounds in a concentration-dependent manner. The Papp values of rhodamine B decreased with increasing concentration of OA, while the Papp values of sodium-fluorescein and FITC-dextrans of 4 kDa increased. The Papp enhanced by 0.1% OA was logarithmically correlated to the molecular weight of model drugs (R(2) = 0.9991). With the 0.02%, 0.05% and 0.1% oleic application, the corneal hydration values were <83%, and Draize scores were <4. CONCLUSION: OA may have potential clinical benefits in improving the ocular drug delivery of both hydrophilic and lipophilic compounds.