Effect of sperminated pullulans on transcorneal permeability of fluorescein sodium

Background Cationic polymers have great potential in improving the permeability through cornea of eye drug.Sperminated derivations are new generation of cationic polymers.Objective This study intended to evaluate the effect of sperminated pullulans (SP) on transcorneal permeability of fluorescein sodium and examine the relationship between the amino groups and the enhancement in vitro.The ocular irritation of SP was also tested both in vivo and in vitro.Methods A total of 9 clean New Zealand white rabbits were randomly divided into control group,Sperminated pullulans(SP)-L group and SP-H group and 6 corneas were included in each group.The freshly excised corneas were immediately mounted in modified Franz perfusion cells under the mixing condition with the corneal epithelium toward the deliver chamber and the endothelium toward the receptor chamber.Fluorescein sodium solution containing free-SP,0.2% SP with 0.124 mmol/g amino (SP-L) or 0.2% SP with 0.578 mmol/g amino (SP-H) was added into the deliver chamber respectively in each group.At 30,60,90,120,150,180,210,240 minutes after addition of fluorescein sodium solution,100 μL of the receptor solution was removed.The concentration of fluorescein sodium was determined by high pressure liquid chromatography.Hydration level of cornea was calculated at the end of each permeation run by the usual gravimetric method.A modified Draize test was carried out to evaluate the eye irritation in vivo.Results The apparent permeability coefficient (Papp) for fluorescein sodium increased by 2.12 fold in SP-L group and 6.87 fold in SP-H group.Fluorescein sodium transcorneal permeation parameters were significantly enhanced in SP-L and SP-H in comparison with control group (P0.05,P0.01),respectively,and that in SP-H group was the more effective enhancer than SP-L group (P0.05).The corneal hydration value was less than 83%.No evident difference was found in corneal hydration value among control group,SP-L group and SP-H group (F=2.650,P=0.130).The scores of Draize test were all lower than 4,indicating that no irritation response of eye occurred after addition of 0.2% SP-L and 0.2% SP-H.Conclusion As a safe and effective permeability enhancer,SP can improve the corneal permeation of hydrophilic drug.The promoting permeation effect of amino in SP is proved to be dose-dependent.