Moderation of cross linkage of sodium alginate-polyethylene oxide films loaded with natamycin for treatment of Aspergillus fumigatus keratitis

The blindness rate of fungal keratitis is high, however, traditional therapy, like eye drops, has poor bioavailability. To make the traditional treatment more effective, new drug-loading system was explored, which can attach to the ocular surface to prolong the release time of natamycin (NATA). Sodium alginate (SA) has attractive properties of biocompatibility, biodegradability, which have been exploited to be natural-origin polymer of drug release. Because of special egg box structure of SA, the sodium ions in the structure can be exchanged with divalent cations through crosslinking, which could control the pore size inside the material and release rate of the loaded drug. Here, we utilized the composite of sodium alginate and polyethylene oxide (PEO) with natamycin loaded through crosslinking with calcium ion ethanol aqueous solution to delay drug release and treat fungal keratitis. The results from experiments proved that the membrane with the slowest rate of drug release was the group with the ratio of ethanol to water 2:1, and the 1% natamycin-loaded films could effectively inhibit the growth of Aspergillus fumigatus. SA-PEO membranes could reduce the inflammatory response. Conclusively, NATA-SA-PEO films could be considered a useful approach to prolong ocular natamycin maintenance and improve the outcome of fungal keratitis.